Unraveling neurotransmitter mediated signaling in horticultural plants under abiotic stress conditions

Introduction

Plants face several environmental stresses, with abiotic factors posing a persistent and progressively intensifying threat to global food security. Owing to their sessile nature, plants are inherently vulnerable to adverse environmental fluctuations, resulting in yield reductions of 50-70%, particularly across Asia (Matthews et al., 1997) [59] . Enhancing plant resilience traits to combat these abiotic stressors has become the need of the hour with critical scientific priority. Under field conditions, plants are frequently subjected to the multiple abiotic stresses, such as drought, heat, salinity, etc. which are often more detrimental to crop growth, development, and productivity than individual stresses alone (Fahad et al., 2017) [21] . Extensive studies on plant-environment interactions have paved the way for targeted interventions designed to optimize the stress-tolerance potential of diverse crops (Gull et al., 2019) [28] . One such promising strategy, the exogenous application of plant growth regulators, hormones, and other biostimulatory compounds, has gained increasing attention for enhancing abiotic stress tolerance (Ahammed et al., 2020a) [107] . In this context, emerging evidence indicates that neurotransmitters constitute an evolutionarily conserved class of bioactive signaling molecules that modulates cellular homeostasis, signal transduction pathways, redox balance and stress-responsive pathways in plants (Roshchina, 2001) [71] .

The widespread distribution of these molecules across biological kingdoms suggests that they function as conserved chemical messengers (Akula & Mukherjee, 2020) [3] . Acetylcholine, catecholamines (such as dopamine and norepinephrine), indoleamines (serotonin and melatonin), and compounds derived from amino acids (like glutamate and γ-aminobutyric acid, or GABA) represent major classes of plant neurotransmitters. It recognized as multifunctional signaling molecules in plants, influencing a wide range of physiological and developmental processes. They regulate organ formation, flowering and reproductive events, membrane ion transport, photosynthetic efficiency, circadian rhythms, photomorphogenic responses, fruit maturation, and plant adaptation to changing environmental conditions (Roshchina, 2016) [72] . A comprehensive understanding of plant neurotransmitters' biosynthesis pathways, signaling mechanisms, and association with established hormonal and redox networks under abiotic stress is still lacking, despite mounting evidence for their regulatory roles. Addressing these gaps is essential for harnessing their potential in developing climate-resilient horticultural crops.

Melatonin

Melatonin

(N-acetyl-5-methoxytryptamine) is a multifunctional indoleamine that present in both animals and plants. First isolated from the human pineal gland (Lerner et al., 1958) [46] , it was initially studied for its regulatory roles in animal physiology. In animals, melatonin is well known for orchestrating circadian and seasonal rhythms, such as those governing migration and reproduction. Subsequently, melatonin was independently detected in higher plants in two pioneering studies involving seeds and edible tissues (Hattori et al., 1995) [30] . Since then, it has been identified across diverse plant taxa, ranging from algae and fungi to a broad spectrum of angiosperms, including both monocotyledonous and dicotyledonous species (Fernández-Alegre et al., 2022) [22] . In plants, melatonin is now regarded as a putative phytohormone and a critical signaling molecule that regulates growth, development, and adaptive responses, particularly under biotic and abiotic stress conditions. Melatonin biosynthesis in plants has been localized primarily to chloroplasts (Zheng et al., 2017) [105] and mitochondria (Wang et al., 2017) [88] , with additional evidence suggesting the possible involvement of cytosol. It is widely distributed among plant organs, with relatively higher concentrations reported in roots, flowers, fruits, seeds, and bulbs. Various horticultural and crop species, including cucumber, tomato, apple, banana, and onion, have been shown to accumulate detectable levels of melatonin (Nawaz et al., 2016) [63] . Functionally, it acts as potent singlet oxygen scavenger (Schaefer & Hardeland, 2009) [75] . It readily traverses cellular membranes and localizes within subcellular compartments such as the nucleus and mitochondria (Tan et al., 2016) [86] . Through direct radical scavenging and enhancement of cellular antioxidant systems, melatonin mitigates oxidative damage, restricts lipid peroxidation, stabilizes membrane integrity, and protects plant tissues against stress-induced injury, thereby functioning as an early protective molecule under adverse environmental conditions.

Biosynthetic pathway of melatonin

In plants melatonin biosynthesis originates from the amino acid tryptophan. In the primary pathway, tryptophan is first decarboxylated by tryptophan decarboxylase (TDC) to produce tryptamine. Tryptamine is subsequently hydroxylated by tryptamine-5-hydroxylase (T5H) to form serotonin (5-hydroxytryptamine, 5-HT) (Kang et al., 2007) [38] . From serotonin, melatonin synthesis proceeds through two alternative routes. In one pathway, serotonin is converted into N-acetylserotonin (NAS) by serotonin-Nacetyltransferase (SNAT), following a mechanism similar to that described in animals (Kang et al., 2013) [37] . In another route, serotonin can be methylated to produce 5methoxytryptamine

(5-MT) via caffeic acid-Omethyltransferase (COMT) (Lee et al., 2014) [45] . Interestingly, SNAT exhibits substrate flexibility. It can directly acetylate tryptamine to form NAS without serotonin as an intermediate and can also acetylate 5-MT to produce melatonin (Byeon et al., 2013) [13] . The final step in melatonin biosynthesis involves the methylation of NAS to produce melatonin. This reaction is catalyzed either by Nacetylserotonin methyltransferase (ASMT) (Park et al., 2013) [65] or by HIOMT (hydroxyindole-Omethyltransferase (Byeon et al., 2014) [108] .

Fig 1: Biosynthetic route of melatonin

Melatonin in abiotic stress response

Building on its strong antioxidant capacity and specific subcellular localization, melatonin plays a pivotal role in regulating plant stress physiology. It enhances photosynthetic efficiency, protects the photosynthetic apparatus from excessive light exposure, preserves chloroplast integrity, and maintains cellular redox homeostasis. Beyond its direct antioxidative function, melatonin also modulates transcriptional regulation by influencing stress-responsive genes and epigenetically associated pathways (Mathur and Pramanik, 2020) [58] . Exogenous application of melatonin has been widely reported to enhance plant tolerance to multiple abiotic stresses, including salinity, drought, low temperature, heavy metal toxicity, and certain biotic challenges. These protective effects are mediated through coordinated interactions with phytohormones, signaling molecules, and transcription factors that collectively regulate adaptive stress responses. In addition to its regulatory functions, melatonin undergoes dynamic metabolism in plants through both enzymatic and non-enzymatic pathways (Zeng et al., 2022) [101] . The precise signaling mechanisms of melatonin-derived metabolites in plants remain largely unresolved. It plays a significant role in mitigating drought-induced oxidative stress by enhancing photosynthetic efficiency, maintaining hormonal balance, regulating stress-responsive gene expression, and promoting physiological adjustments. It strengthens antioxidant defense systems, sustains cellular water status, and ultimately contributes to improved stress tolerance and yield stability. Similarly, in Hibiscus, melatonin increases chlorophyll content and photosynthetic performance, partly through interaction with salicylic acid signaling (Yan et al., 2023) [95] , while in coffee plants it reduces chlorophyll degradation and electrolyte leakage under stress conditions (Cherono et al., 2021) [15] . In Salvia species, melatonin not only alleviates stress injury but also enhances essential oil yield and composition (Bidabadi et al., 2020) [10] . Foliar application of melatonin in Moringa oleifera improves yield and amino acid composition, thereby reducing the detrimental effects of drought stress (Sadak et al., 2020) [73] . Beyond drought stress, melatonin also confers tolerance to salinity stress through multiple physiological and molecular mechanisms. Exogenous treatment increases fresh and dry biomass, limits chlorophyll degradation, maintains lower cellular sodium accumulation, and enhances antioxidant enzyme activity under saline conditions. It further induces the expression of salt stress-responsive genes, including the vacuolar Na⁺/H⁺ antiporter NHX1 and the potassium transporter AKT1. In tomato, melatonin application alleviates combined salinity and heat stress by reducing ROS accumulation, improving photosynthesis, maintaining stomatal function, and enhancing overall plant growth (Martinez et al., 2018; Khan et al., 2024) [57,40] . Similar protective effects have been reported in Ranunculus repens, where 200 μM melatonin improved growth attributes, enhanced peroxidase activity, reduced ROS levels, and delayed flower bud emergence under salinity stress (Eisa et al., 2023) [19] . In tomato cultivars 'Roma' and 'FM9', melatonin mitigated salt toxicity by improving antioxidant capacity, growth parameters, and ion homeostasis (Ali et al., 2021) [5] . Likewise, melatonin priming in potato alleviated salt-induced damage by enhancing stolon formation, maintaining tissue water content, regulating ion balance, and increasing the accumulation of proline, flavonoids, and carotenoids (Efimova et al., 2023) [18] . Furthermore, melatonin treatment improves seed germination under saline-alkaline conditions by stimulating antioxidant enzyme activities, promoting osmolyte accumulation, and reducing oxidative stress (Wang et al., 2023) [89] . Melatonin was found to alleviate chlorosis, decrease chlorophyll degradation, and stabilize photosynthetic rate by scavenging reactive oxygen species (ROS) and protecting chloroplasts in apple plants (Zheng et al., 2021) [104] . In tomato, melatonin treatment in plants affected cell wall polysaccharide biosynthesis, glutathione metabolism, and redox homeostasis, leading to increased retention of chromium in the cell wall, improved chelation and sequestration of chromium, and enhanced antioxidant capacity to mitigate oxidative stress (Yang et al., 2023) [96] . Overall, these findings establish melatonin as a key regulator of plant stress adaptation, coordinating metabolic stability, cellular protection, and growth maintenance under adverse conditions. A summary of the studied plant species, stress types, and corresponding physiological roles of melatonin is presented in Table 1. [93] Solanum lycopersicum Drought Promotes cuticle formation Ding et al., 2018 [17] Capsicum annuum Salinity Increases the active of iron, Potassium, endogenous Nitic oxide and Hydrogen sulphide Kaya et al., 2020 [29] Malus hupehensis Alkalinity Regulates polyamine synthesis Gong et al., 2017 [27] Prunus persica Drought tolerance, reduced chilling injury, post-harvest improvement Gao et al., 2016 [23] Actinidia deliciosa Thermotolerance Promotes antioxidant enzyme and glutathione s-transferase transcription Liang et al., 2018 [49] Limonium bicolor Salinity Improved seed germination Li et al., 2019 [47] 3. Acetylcholine Acetylcholine (ACh) is an evolutionarily conserved bioactive molecule detected across diverse life forms, including bacteria, algae, fungi, mosses, and higher plants, indicating its early phylogenetic origin and fundamental biological significance. Although traditionally associated with neurotransmission in animals, accumulating evidence demonstrates that ACh and its metabolic enzymes are widely distributed throughout the plant kingdom. Early studies in Urtica dioica suggested a role for ACh in regulating water relations and photosynthetic processes. Subsequent biochemical investigations confirmed the presence of ACh in multiple plant species and tissues, including mungbean roots, maize, pea, spinach, sunflower, and blue-green algae. Quantitative analyses further revealed that ACh levels are higher in actively growing tissues, supporting its involvement in developmental regulation. ACh as a non-neuronal signaling molecule of functional relevance in plants.

Biosynthesis and metabolic reprogramming

In plants, ACh is synthesized from choline and acetylcoenzyme A (acetyl-CoA) through a single-step enzymatic reaction catalyzed by choline acetyltransferase (ChAT), particularly active in young and metabolically dynamic tissues. Its cellular concentration is tightly controlled by acetylcholinesterase (AChE), which hydrolyzes ACh into choline and acetate (Sarangle et al., 2024) [74] . Environmental factors modulate ACh biosynthesis. Light quality, in particular, plays a regulatory role, as red light enhances precursor incorporation into ACh compared with far-red light, suggesting phytochrome-mediated control. [109] . Computational studies have also identified potential nAChR homologs in tomato (Solanum lycopersicum) (Bamel and Mondal, 2023) [9] , bolstering the notion of receptor-mediated cholinergic signaling within plants. ACh influences membrane permeability and ion fluxes involving H⁺, K⁺, Na⁺, Ca²⁺, and Cl⁻, thus affecting membrane depolarization, intracellular Ca²⁺ dynamics, and long-distance electrical signaling (Palee et al., 2016) [64] . These ion-mediated mechanisms are crucial for the initiation of plant action potentials and systemic signaling (Sukhov et al., 2011) [84] . Beyond its roles in electrophysiology, ACh has been associated with communication from roots to shoots (Brenner et al., 2006) [12] , the induction of rooting (Bamel et al., 2007) [8] , the progression of seedling development, the regulation of stomata, and the translocation of carbohydrates (Sugiyama et al., 2011) [82] . Most studies on acetylcholine in plants have been conducted in agricultural and fodder crops, whereas investigations in horticultural crops remain limited.

Dopamine

Dopamine is a catecholamine present in both animals and plants. In humans, it plays essential roles in reward signaling, motor control, and hormonal regulation, and its dysregulation is associated with neurological disorders such as Parkinson's disease, schizophrenia, and depression. In plants, dopamine has emerged as an important growthpromoting and stress-mitigating molecule. Increasing evidence indicates that dopamine enhances plant tolerance to abiotic stresses including drought, salinity, nutrient imbalance, chilling, and oxidative stress (Allen, 2003; Liu et al., 2020) [6,54] . Dopamine possesses strong antioxidant properties and participates in multiple physiological processes through interactions with plant hormones and signaling networks. Its levels fluctuate during plant development and typically increase under stress conditions (Liang et al., 2017; Zhang et al., 2022) [50,[102][103] .

Biosynthesis of dopamine

Dopamine (C₈H₁₁NO₂; molecular weight 153.18) is a nitrogen-containing, light-sensitive compound that readily oxidizes in the presence of oxygen (Howe & Dombeck, 2016) [31] . In plants, catecholamine biosynthesis resembles that of mammals and originates from the amino acid tyrosine (Kulma & Szopa, 2007) [42] . However, enzymatic routes and regulation may vary among species. In plants, dopamine is synthesized in the cytoplasm from the amino acid tyrosine via two principal pathways.

In the decarboxylation pathway, tyrosine is first decarboxylated by tyrosine decarboxylase (TYDC) to form tyramine, which is subsequently hydroxylated by monophenol hydroxylase (MH) to produce dopamine. In the hydroxylation pathway, tyrosine is initially hydroxylated by tyrosine hydroxylase (TH) to generate L-DOPA, followed by decarboxylation by DOPA decarboxylase (DD) to form dopamine (Facchini & De Luca, 1995) [20] . Dopamine may further be converted into norepinephrine and epinephrine via dopamine β-hydroxylase-like and phenylethanolamine N-methyltransferase-like enzymes. Environmental factors significantly influence dopamine biosynthesis (Liang et al., 2017) [50] . [49,51,24] . Dopamine also enhanced water-use efficiency (WUE), increased sucrose and organic acid accumulation, and modulated Ca²⁺ signaling pathways. Similarly, in Solanum lycopersicum, dopamine improved drought tolerance by upregulating antioxidant enzymes (SOD and CAT), reducing ethylene production, maintaining membrane integrity, and enhancing root biomass (Akcay et al., 2024) [2] . Salinity stress disturbs ion balance and induces osmotic and oxidative damage. Dopamine regulates ion homeostasis by enhancing K⁺/Na⁺ and Ca²⁺/Na⁺ ratios and upregulating salt overly sensitive (SOS) pathway genes. It also promoted uptake of essential nutrients (N, P, K, S, Cu, Mn) and suppressed toxic ion accumulation. In tomato, dopamine increased indole-3-acetic acid (IAA) levels, reduced ABA accumulation, regulated sugar metabolism, and improved salinity tolerance (Yildirim et al., 2024) [97] . Chilling temperatures impair membrane stability and photosynthesis.

In Citrullus lanatus, dopamine application enhanced chlorophyll content, proline accumulation, antioxidant enzyme activity, and polyamine metabolism, collectively improving chilling tolerance (Jiao et al., 2021) [33] . In banana (Musa sapientum), dopamine treatment increased endogenous dopamine levels, suppressed chlorophyll degradation genes (MDC, PPH, PaO, RCCR), and enhanced antioxidant enzyme activity, thereby reducing oxidative damage during chilling (Ali et al., 2023) [4] . Table 2 presents a compilation of the documented horticultural species, their corresponding abiotic stress factors, and the physiological mechanisms modulated by dopamine. Overall, dopamine functions as a multifunctional growth regulator and stressmitigating molecule in horticultural plants. These findings highlight its potential application as a sustainable biostimulant to improve horticultural crop productivity under changing climatic conditions. [4] 5. GABA γ-Aminobutyric acid (GABA) is a four-carbon, nonproteinogenic amino acid widely distributed in autotrophic and heterotrophic organisms. It was first identified in potato tubers (Den et al., 1947) and has subsequently been detected in plants, animals, fungi, and bacteria. GABA serves as a dual role as a metabolite and/or as a signalling molecule in plant growth, development, and stress responses (Bouche and Fromm 2004; Roberts, 2007) [11,70] . GABA is rapidly and substantially accumulated in plants in response to both biotic and abiotic stress conditions (Scholz et al., 2015) [76] . GABA acts as a priming agent by triggering diverse defense-associated signaling pathways in response to adverse environmental cues (Kinnersley and Turano, 2000) [41] .

Biosynthesis of GABA

Chemically, GABA (C₄H₉NO₂; 103 Da) is synthesized primarily through the decarboxylation of L-glutamate via the GABA shunt pathway, catalyzed by glutamate decarboxylase (GAD) (Xu and Hu et al., 2014) [92] . In addition to this major pathway, GABA can also be produced from polyamines such as putrescine and spermidine through the action of diamine oxidase and polyamine oxidase [Shelp et al., 2012] [78] . Within mitochondria, GABA is converted into succinic semialdehyde by GABA transaminase (GABA-T), which is subsequently oxidized to succinate by succinic semialdehyde dehydrogenase (SSADH). Succinate then enters the tricarboxylic acid (TCA) cycle, thereby linking the GABA shunt to central carbon metabolism. The mitochondrial membrane transporter GABA permease (GABA-P) facilitates the transport of cytosolic GABA into mitochondria, integrating the GABA shunt with the TCA cycle to provide energy and carbon skeletons (Michaeli et al., 2011) [60] . The key enzymes of the GABA shunt such as glutamate GAD), GABA-T, and SSADH play crucial roles in maintaining ion homeostasis (Su et al., 2019) [81] , enhancing abiotic stress tolerance (Jalil et al., 2017; Sita and Kumar, 2020) [32,79] , and regulating plant growth, development, and senescence. GAD is a Ca²⁺/calmodulin-binding protein whose activity is stimulated by elevated cytosolic Ca²⁺ levels and neutral pH in intact plants (Snedden et al., 1995) [80] . GABA receptor genes in plants encode structural domains homologous to those found in animals (Lacombe et al., 2001) [44] . Under stress conditions, GABA improves morphological and physiological traits, including enhanced photosynthetic efficiency and increased accumulation of osmoprotectants such as proline (Ma et al., 2019) [55] . It also regulates polyamine metabolism (Seifikalhor et al., 2020) [77] and mitigates oxidative damage by activating antioxidant defense systems and modulating antioxidant enzyme gene expression (Kumar et al., 2019) [43] . Under salt stress, GABA functions as a non-toxic osmolyte, reduces ROS accumulation, modulates the ascorbate-glutathione cycle, and improves saline-alkali stress tolerance (Jin et al., 2019) [35] . In addition to drought, GABA has been reported to alleviate salinity, heat stress, chilling, low-temperature, and heavy metal stress, as summarised in Table 3. [83] 6. Future perspectives Future studies should aim to clarify the exact perception and signaling pathways of melatonin, acetylcholine, dopamine, and GABA in plants, with a specific focus on identifying distinct receptors, transport systems, and downstream regulatory networks. A heightened focus on understanding their interactions with classical phytohormones and redox pathways is necessary to elucidate how these molecules fit into larger stress-response frameworks. Innovations in omics technologies, gene-editing techniques, and metabolic engineering present valuable opportunities to modify key biosynthetic genes and boost endogenous levels for enhanced stress resilience. Furthermore, extensive field trials and the creation of stable, economical formulations are crucial for converting laboratory insights into practical horticultural uses. In summary, the integration of neurotransmitter-focused strategies with breeding and sustainable crop management methods could greatly aid in the establishment of climate-resilient horticultural systems.

Conclusions

Neurotransmitter-like molecules, once thought to be exclusive to animal systems, are now acknowledged as essential components in the physiology of plant stress. Melatonin, acetylcholine, dopamine, and GABA serve as multifunctional regulators that harmonize antioxidant defense, ion balance, hormonal signaling, photosynthetic efficiency, and gene expression when plants face abiotic stress. Their biosynthetic pathways are finely tuned and responsive to environmental stimuli, allowing for a dynamic response to changing stress conditions. Experimental findings across various horticultural species indicate that the external application or internal enhancement of these molecules significantly alleviates drought, salinity, temperature stress, heavy metal toxicity, and nutrient imbalances. By influencing ROS scavenging systems, MAPK signaling pathways, transcription factors, osmolyte accumulation, and metabolic processes, these compounds play a crucial role in enhancing growth, ensuring yield stability, and boosting stress resilience. Despite notable advancements, there are still gaps in our understanding of receptor-mediated perception mechanisms, downstream signaling elements, and the long-term effectiveness in field conditions.

References

1. Aghdam MS, Naderi R, Jannatizadeh A, Sarcheshmeh MAA, Babalar M. Enhancement of postharvest chilling tolerance of anthurium cut flowers by γ-aminobutyric acid (GABA) treatments. Scientia Horticulturae. 2016;198:52-60.
2. Akcay UC, Gencay R, Koc FZ. Effect of dopamine and progesterone on the physiological and molecular responses of tomato seedlings to drought and salt stress. Cogent Food and Agriculture. 2024;10(1):2321308.
3. Akula R, Mukherjee S. New insights on neurotransmitters signaling mechanisms in plants. Plant Signaling and Behavior. 2020;15(6):1737450.
4. Ali AF, Hatamnia AA, Malekzadeh P, Sayyari M, Aghdam MS. Exogenous dopamine ameliorates chilling injury in banana fruits by enhancing endogenous dopamine and glycine betaine accumulation and promoting ROS scavenging system activity. Postharvest Biology and Technology. 2023;205:112521.
5. Ali M, Kamran M, Abbasi GH, Saleem MH, Ahmad S, Parveen A, et al. Melatonin-induced salinity tolerance International Journal of Advanced Biochemistry Research https://www.biochemjournal.com by ameliorating osmotic and oxidative stress in the seedlings of two tomato (Solanum lycopersicum L.) cultivars. Journal of Plant Growth Regulation. 2021;40(5):2236-2248.
6. Allen JF. Superoxide as an obligatory, catalytic intermediate in photosynthetic reduction of oxygen by adrenaline and dopamine. Antioxidants and Redox Signaling. 2003;5(1):7-14.
7. Back K. Melatonin metabolism, signaling and possible roles in plants. The Plant Journal. 2021;105(2):376-391.
8. Bamel K, Gupta SC, Gupta R. Acetylcholine causes rooting in leaf explants of in vitro raised tomato (Lycopersicon esculentum Miller) seedlings. Life Sciences. 2007;80(24-25):2393-2396.
9. Bamel K, Mondal N. In vitro culture using nicotine and d-tubocurarine and in silico analysis depict the presence of acetylcholine receptor (AChR) in tomato (Solanum lycopersicum L.). In Vitro Cellular and Developmental Biology -Plant. 2023;59(1):39-48.
10. Bidabadi SS, VanderWeide J, Sabbatini P. Exogenous melatonin improves glutathione content, redox state and increases essential oil production in two Salvia species under drought stress. Scientific Reports. 2020;10(1):6883.
11. Bouche N, Fromm H. GABA in plants: just a metabolite? Trends in Plant Science. 2004;9(3):110115.
12. Brenner ED, Stahlberg R, Mancuso S, Vivanco J, Baluška F, Van Volkenburgh E. Plant neurobiology: an integrated view of plant signaling. Trends in Plant Science. 2006;11(8):413-419.
13. Byeon Y, Lee K, Park YI, Park S, Back K. Molecular cloning and functional analysis of serotonin Nacetyltransferase from the cyanobacterium Synechocystis sp. PCC 6803. Journal of Pineal Research. 2013;55(4):371-376.
14. Cheng B, Li Z, Liang L, Cao Y, Zeng W, Zhang X, et al. The γ-aminobutyric acid (GABA) alleviates salt stress damage during seed germination of white clover associated with Na⁺/K⁺ transportation, dehydrins accumulation and stress-related genes expression. International Journal of Molecular Sciences. 2018;19(9):2520.
15. Cherono S, Ntini C, Wassie M, Mollah MD, Belal MA, Ogutu C, et al. Exogenous application of melatonin improves drought tolerance in coffee by regulating photosynthetic efficiency and oxidative damage. Journal of the American Society for Horticultural Science. 2021;146(1):24-32.
16. Dent CE, Stepka W, Steward FC. Detection of the free amino acids of plant cells by partition chromatography. Nature. 1947;160(4072):682-683.
17. Ding F, Wang G, Wang M, Zhang S. Exogenous melatonin improves tolerance to water deficit by promoting cuticle formation in tomato plants. Molecules. 2018;23:E1605.
18. Efimova MV, Danilova ED, Zlobin IE, Kolomeichuk LV, Murgan OK, Boyko EV, et al. Priming potato plants with melatonin protects stolon formation under delayed salt stress by maintaining photochemical function of photosystem II, ionic homeostasis and activating the antioxidant system. International Journal of Molecular Sciences. 2023;24(7):6134.
19. Eisa EA, Honfi P, Tilly-Mándy A, Mirmazloum I. Exogenous melatonin application induced morphophysiological and biochemical regulations conferring salt tolerance in Ranunculus asiaticus L. Horticulturae. 2023;9(2):228.
20. Facchini PJ, De Luca V. Phloem-specific expression of tyrosine/dopa decarboxylase genes and the biosynthesis of isoquinoline alkaloids in opium poppy. The Plant Cell. 1995;7(11):1811-1821.
21. Fahad S, Bajwa AA, Nazir U, Anjum SA, Farooq A, Zohaib A, et al. Crop production under drought and heat stress: plant responses and management options. Frontiers in Plant Science. 2017;8:1147.
22. Fernández-Alegre E, Lacalle E, Soriano-Úbeda C, González-Montaña JR, Domínguez JC, Casao A, et al. Bos taurus and Cervus elaphus as nonseasonal/seasonal models for the role of melatonin receptors in the spermatozoon. International Journal of Molecular Sciences. 2022;23(11):6284.
23. Gao H, Zhang ZK, Chai HK, Cheng N, Yang Y, Wang DN, et al. Melatonin treatment delays postharvest senescence and regulates reactive oxygen species metabolism in peach fruit. Postharvest Biology and Technology. 2016.
24. Gao T, Liu X, Shan L, Wu Q, Liu Y, Zhang Z, et al. Dopamine and arbuscular mycorrhizal fungi act synergistically to promote apple growth under salt stress. Environmental and Experimental Botany. 2020;178:104159.
25. Gao T, Liu Y, Liu X, Zhao K, Shan L, Wu Q, et al. Exogenous dopamine and overexpression of the dopamine synthase gene MdTYDC alleviated apple replant disease. Tree Physiology. 2021;41(8):15241541.
26. Golnari S, Vafaee Y, Nazari F, Ghaderi N. Gammaaminobutyric acid (GABA) and salinity impacts antioxidative response and expression of stress-related genes in strawberry cv. Aromas. Brazilian Journal of Botany. 2021;44(3):639-651.
27. Gong X, Shi S, Dou F, Song Y, Ma F. Exogenous melatonin alleviates alkaline stress in Malus hupehensis Rehd. by regulating the biosynthesis of polyamines. Molecules. 2017;22:1542.
28. Gull A, Lone AA, Wani NU. Biotic and abiotic stresses in plants. In: Abiotic and biotic stress in plants. IntechOpen; 2019.
29. Hartmann E, Gupta R. Acetylcholine as a signaling system in plants. In: Second messengers in plant growth and development. 1989;6:257.
30. Hattori A, Herbert DC, Vaughan MK, Yaga K, Reiter RJ. Melatonin inhibits luteinizing hormone releasing hormone induction of LH release from fetal rat pituitary cells. Neuroscience Letters. 1995;184(2):109-112.
31. Howe MW, Dombeck DA. Rapid signalling in distinct dopaminergic axons during locomotion and reward. Nature. 2016;535(7613):505-510.
32. Jalil SU, Ahmad I, Ansari MI. Functional loss of GABA transaminase (GABA-T) expressed early leaf senescence under various stress conditions in Arabidopsis thaliana. Current Plant Biology. 2017;9:11-22.
33. Jiao C, Lan G, Sun Y, Wang G, Sun Y. Dopamine alleviates chilling stress in watermelon seedlings via modulation of proline content, antioxidant enzyme activity and polyamine metabolism. Journal of Plant Growth Regulation. 2021;40(1):277-292.
34. Jiao C. γ-Aminobutyric acid boosts chilling tolerance by promoting the methionine sulfoxide reductasethioredoxin reductase system in peach fruit. Horticulture, Environment, and Biotechnology. 2022;63(3):353-361.
35. Jin X, Liu T, Xu J, Gao Z, Hu X. Exogenous GABA enhances muskmelon tolerance to salinity-alkalinity stress by regulating redox balance and chlorophyll biosynthesis. BMC Plant Biology. 2019;19(1):48.
36. Kalhor MS, Aliniaeifard S, Seif M, Asayesh EJ, Bernard F, Hassani B, et al. Enhanced salt tolerance and photosynthetic performance: implication of γaminobutyric acid application in salt-exposed lettuce (Lactuca sativa L.) plants. Plant Physiology and Biochemistry. 2018;130:157-172.
37. Kang K, Lee K, Park S, Byeon Y, Back K. Molecular cloning of rice serotonin N-acetyltransferase, the penultimate gene in plant melatonin biosynthesis. Journal of Pineal Research. 2013;55(1):7-13.
38. Kang S, Kang K, Lee K, Back K. Characterization of tryptamine 5-hydroxylase and serotonin synthesis in rice plants. Plant Cell Reports. 2007;26(11):2009-2015.
39. Kaya C, Higgs D, Ashraf M, Alyemeni MN, Ahmad P. Integrative roles of nitric oxide and hydrogen sulfide in melatonin-induced tolerance of pepper (Capsicum annuum L.) plants to iron deficiency and salt stress alone or in combination. Physiologia Plantarum. 2020;168:256-277.
40. Khan S, Saify S, Sofo A, Khan NA. The mechanisms of melatonin action in shielding photosynthesis during heat stress. CABI Reviews. 2024;19(1).
41. Kinnersley AM, Turano FJ. Gamma-aminobutyric acid (GABA) and plant responses to stress. Critical Reviews in Plant Sciences. 2000;19(6):479-509.
42. Kulma A, Szopa J. Catecholamines are active compounds in plants. Plant Science. 2007;172(3):433440.
43. Kumar N, Gautam A, Dubey AK, Ranjan R, Pandey A, Kumari B, et al. GABA-mediated reduction of arsenite toxicity in rice seedlings through modulation of fatty acids, stress-responsive amino acids and polyamine biosynthesis. Ecotoxicology and Environmental Safety. 2019;173:15-27.
44. Lacombe B, Becker D, Hedrich R, DeSalle R, Hollmann M, Kwak JM, et al. The identity of plant glutamate receptors. Science. 2001;292(5521):14861487.
45. Lee HY, Byeon Y, Lee K, Lee HJ, Back K. Cloning of Arabidopsis serotonin N-acetyltransferase and its role with caffeic acid O-methyltransferase in the biosynthesis of melatonin in vitro despite their different subcellular localizations. Journal of Pineal Research. 2014;57(4):418-426.
46. Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocytes. Journal of the American Chemical Society. 1958;80(10):2587.
47. Li J, Zhao C, Zhang M, Yuan F, Chen M. Exogenous melatonin improves seed germination in Limonium bicolor under salt stress. Plant Signaling and Behavior. 2019;14:1659705.
48. Li X, Wei JP, Scott ER, Liu JW, Guo S, Li Y, et al. Exogenous melatonin alleviates cold stress by promoting antioxidant defense and redox homeostasis in Camellia sinensis L. Molecules. 2018;23:165.
49. Liang B, Gao T, Zhao Q, Ma C, Chen Q, Wei Z, et al. Effects of exogenous dopamine on the uptake, transport and resorption of apple ionome under moderate drought. Frontiers in Plant Science. 2018;9:755.
50. Liang B, Li C, Ma C, Wei Z, Wang Q, Huang D, et al. Dopamine alleviates nutrient deficiency-induced stress in Malus hupehensis. Plant Physiology and Biochemistry. 2017;119:346-359.
51. Liang D, Gao F, Ni Z, Lin L, Deng Q, Tang Y, et al. Melatonin improves heat tolerance in kiwifruit seedlings through promoting antioxidant enzymatic activity and glutathione S-transferase transcription. Molecules. 2018;23(3):584.
52. Liu C, Wang H, Zhang X, Ma F, Guo T, Li C. Activation of the ABA signal pathway mediated by GABA improves the drought resistance of apple seedlings. International Journal of Molecular Sciences. 2021;22(23):12676.
53. Liu Z, Ji Z, Han Y, Sun Y. The mitigation effects of exogenous dopamine treatment on continuous cropping obstacles in watermelon. Journal of Soil Science and Plant Nutrition. 2023;23(3):4233-4249.
54. Liu Q, Gao T, Liu W, Liu Y, Zhao Y, Liu Y, et al. Functions of dopamine in plants: a review. Plant Signaling and Behavior. 2020;15(12):1827782.
55. Ma Y, Wang P, Wang M, Sun M, Gu Z, Yang R. GABA mediates phenolic compounds accumulation and enhancement of the antioxidant system in germinated hulless barley under NaCl stress. Food Chemistry. 2019;270:593-601.
56. Malekzadeh P, Khara J, Heydari R. Alleviating effects of exogenous gamma-aminobutyric acid on tomato seedlings under chilling stress. Physiology and Molecular Biology of Plants. 2014;20(1):133-137.
57. Martinez V, Nieves-Cordones M, Lopez-Delacalle M, Rodenas R, Mestre TC, Garcia-Sanchez F, et al. Tolerance to stress combination in tomato plants: new insights into the protective role of melatonin. Molecules. 2018;23(3):535.
58. Mathur P, Pramanik S. Prospective role of melatonin in signaling and alleviation of stress in plants. In: Neurotransmitters in Plant Signaling and Communication. Cham: Springer International Publishing; 2020. p.213-240.
59. Matthews RB, Kropff MJ, Horie T, Bachelet D. Simulating the impact of climate change on rice production in Asia and evaluating options for adaptation. Agricultural Systems. 1997;54(3):399-425.
60. Michaeli S, Fait A, Lagor K, Nunes-Nesi A, Grillich N, Yellin A, et al. A mitochondrial GABA permease connects the GABA shunt and the TCA cycle and is essential for normal carbon metabolism. The Plant Journal. 2011;67(3):485-498.
61. Mohammadi M, Aelaei M, Saidi M. Pre-harvest spray of GABA and spermine delays postharvest senescence and alleviates chilling injury of gerbera cut flowers during cold storage. Scientific Reports. 2021;11(1):14166.
62. Nabaei N, Amooaghaie R. Interactive effect of melatonin and sodium nitroprusside on seed germination and seedling growth of Catharanthus roseus under cadmium stress. Russian Journal of Plant Physiology. 2019;66:128-139.
63. Nawaz MA, Huang Y, Bie Z, Ahmed W, Reiter RJ, Niu M, et al. Melatonin: current status and future perspectives in plant science. Frontiers in Plant Science. 2016;6:1230.
64. Palee S, Apaijai N, Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. Acetylcholine attenuates hydrogen peroxide-induced intracellular calcium dyshomeostasis through both muscarinic and nicotinic receptors in cardiomyocytes. Cellular Physiology and Biochemistry. 2016;39(1):341-349.
65. Park S, Byeon Y, Back K. Functional analyses of three ASMT gene family members in rice plants. Journal of Pineal Research. 2013;55(4):409-415.
66. Posmyk MM, Janas KM. Melatonin in plants. Acta Physiologiae Plantarum. 2009;31:1-11.
67. Posmyk MM, Kuran H, Marciniak K, Janas KM. Presowing seed treatment with melatonin protects red cabbage seedlings against toxic copper ion concentrations. Journal of Pineal Research. 2008;45(1):24-31.
68. Ren T, Zheng P, Zhang K, Liao J, Xiong F, Shen Q, et al. Effects of GABA on polyphenol accumulation and antioxidant activities in tea plants (Camellia sinensis L.) under heat stress conditions. Plant Physiology and Biochemistry. 2021;159:363-371.
69. Rezaei-Chiyaneh E, Seyyedi SM, Ebrahimian E, Moghaddam SS, Damalas CA. Exogenous application of gamma-aminobutyric acid (GABA) alleviates the effect of water deficit stress in black cumin (Nigella sativa L.). Industrial Crops and Products. 2018;112:741-748.
70. Roberts MR. Does GABA act as a signal in plants? Hints from molecular studies. Plant Signaling and Behavior. 2007;2(5):408-409.
71. Roshchina VV. Neurotransmitters in plant life. Boca Raton: CRC Press; 2001.
72. Roshchina VV. New trends and perspectives in the evolution of neurotransmitters in microbial, plant, and animal cells. In: Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health. 2016. p.25-77.
73. Sadak MS, Abdalla AM, Abd Elhamid EM, Ezzo MI. Role of melatonin in improving growth, yield quantity and quality of Moringa oleifera L. plant under drought stress. Bulletin of the National Research Centre. 2020;44(1):18.
74. Sarangle Y, Bamel K, Purty RS. Identification of acetylcholinesterase-like gene family and its expression under salinity stress in Solanum lycopersicum. Journal of Plant Growth Regulation. 2024;43(3):940-960.
75. Schaefer M, Hardeland R. The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavenger. Journal of Pineal Research. 2009;46(1):49-52.
76. Scholz SS, Reichelt M, Mekonnen DW, Ludewig F, Mithöfer A. Insect herbivory-elicited GABA accumulation in plants is a wound-induced, direct, systemic, and jasmonate-independent defense response. Frontiers in Plant Science. 2015;6:1128.
77. Seifikalhor M, Aliniaeifard S, Bernard F, Seif M, Latifi M, Hassani B, et al. γ-Aminobutyric acid confers cadmium tolerance in maize plants by concerted regulation of polyamine metabolism and antioxidant defense systems. Scientific Reports. 2020;10(1):3356.
78. Shelp BJ, Bozzo GG, Trobacher CP, Zarei A, Deyman KL, Brikis CJ. Contribution of putrescine to 4aminobutyrate (GABA) production in response to abiotic stress. Plant Science. 2012;193:130-135.
79. Sita K, Kumar V. Role of gamma-aminobutyric acid (GABA) against abiotic stress tolerance in legumes: a review. Plant Physiology Reports. 2020;25(4):654-663.
80. Snedden WA, Arazi T, Fromm H, Shelp BJ. Calcium/calmodulin activation of soybean glutamate decarboxylase. Plant Physiology. 1995;108(2):543.
81. Su N, Wu Q, Chen J, Shabala L, Mithöfer A, Wang H, et al. GABA operates upstream of H⁺-ATPase and improves salinity tolerance in Arabidopsis by enabling cytosolic K⁺ retention and Na⁺ exclusion. Journal of Experimental Botany. 2019;70(21):6349-6361.
82. Sugiyama KI, Tezuka T. Acetylcholine promotes the emergence and elongation of lateral roots of Raphanus sativus. Plant Signaling and Behavior. 2011;6(10):1545-1553.
83. Suhel M, Husain T, Prasad SM, Singh VP. GABA requires nitric oxide for alleviating arsenate stress in tomato and brinjal seedlings. Journal of Plant Growth Regulation. 2023;42(2):670-683.
84. Sukhov V, Nerush V, Orlova L, Vodeneev V. Simulation of action potential propagation in plants. Journal of Theoretical Biology. 2011;291:47-55.
85. Świędrych A, Stachowiak J, Szopa J. Catecholamine potentiates starch mobilization in transgenic potato tubers. Plant Physiology and Biochemistry. 2004;42(2):103-109.
86. Tan DX, Manchester LC, Qin L, Reiter RJ. Melatonin: a mitochondrial targeting molecule involving mitochondrial protection and dynamics. International Journal of Molecular Sciences. 2016;17(12):2124.
87. Tan DX, Zanghi BM, Manchester LC, Reiter RJ. Melatonin identified in meats and other foodstuffs: potentially nutritional impact. Journal of Pineal Research. 2014;57:213-218.
88. Wang L, Feng C, Zheng X, Guo Y, Zhou F, Shan D, et al. Plant mitochondria synthesize melatonin and enhance the tolerance of plants to drought stress. Journal of Pineal Research. 2017;63(3):e12429.
89. Wang Q, Xu W, Ren C, Zhan C, Wang C, Li J, et al. Physiological and biochemical mechanisms of exogenous melatonin regulation of saline-alkali tolerance in oats. Agronomy. 2023;13(5):1327.
90. Wang Y, Luo Z, Huang X, Yang K, Gao S, Du R. Effect of exogenous γ-aminobutyric acid (GABA) treatment on chilling injury and antioxidant capacity in banana peel. Scientia Horticulturae. 2014;168:132-137.
91. Wang Y, Zhang Z, Wang X, Yuan X, Wu Q, Chen S, et al. Exogenous dopamine improves apple fruit quality via increasing flavonoids and soluble sugar contents. Scientia Horticulturae. 2021;280:109903.
92. Xu JG, Hu QP. Changes in γ-aminobutyric acid content and related enzyme activities in Jindou 25 soybean (Glycine max L.) seeds during germination. LWT - Food Science and Technology. 2014;55(1):341-346.
93. Xu W, Cai SY, Zhang Y, Wang Y, Ahammed GJ, Xia XJ, et al. Melatonin enhances thermotolerance by promoting cellular protein protection in tomato plants. Journal of Pineal Research. 2016;61(4):457-469.
94. Xu XD, Sun Y, Sun B, Zhang J, Guo XQ. Effects of exogenous melatonin on active oxygen metabolism of cucumber seedlings under high temperature stress. Ying Yong Sheng Tai Xue Bao. 2010;21:1295-1300.
95. Yan D, Wang J, Lu Z, Liu R, Hong Y, Su B, et al. Melatonin-mediated enhancement of photosynthetic capacity and photoprotection improves salt tolerance in wheat. Plants. 2023;12(23):3984.
96. Yang X, Ren J, Li J, Lin X, Xia X, Yan W, et al. Metaanalysis of the effect of melatonin application on abiotic stress tolerance in plants. Plant Biotechnology Reports. 2023;17(1):39-52.
97. Yildirim E, Ekinci M, Turan M, Yuce M, Ors S, Araz O, et al. Exogenous dopamine mitigates the effects of salinity stress in tomato seedlings by alleviating oxidative stress and regulating phytohormones. Acta Physiologiae Plantarum. 2024;46(5):59.
98. Yogeswara IB, Maneerat S, Haltrich D. Glutamate decarboxylase from lactic acid bacteria: a key enzyme in GABA synthesis. Microorganisms. 2020;8(12):1923.
99. Yong B, Xie H, Li Z, Li YP, Zhang Y, Nie G, et al. Exogenous application of GABA improves PEGinduced drought tolerance positively associated with GABA-shunt, polyamines, and proline metabolism in white clover. Frontiers in Physiology. 2017;8:1107.
100. Zeng W, Hassan MJ, Kang D, Peng Y, Li Z. Photosynthetic maintenance and heat shock protein accumulation relating to γ-aminobutyric acid (GABA)- regulated heat tolerance in creeping bentgrass (Agrostis stolonifera). South African Journal of Botany. 2021;141:405-413.
101. Zeng W, Mostafa S, Lu Z, Jin B. Melatonin-mediated abiotic stress tolerance in plants. Frontiers in Plant Science. 2022;13:847175.
102. Zhang Y, Zhang M, Li T, Zhang X, Wang L. Enhance production of γ-aminobutyric acid (GABA) and improve the function of fermented quinoa by cold stress. Foods. 2022;11(23):3908.
103. Zhang ZJ, Zhang J. Tissue distribution and changes in dopamine during development and stress responses in Malus germplasm. Journal of Integrative Agriculture. 2022;21(3):710-724.
104. Zheng S, Zhu Y, Liu C, Zhang S, Yu M, Xiang Z, et al. Molecular mechanisms underlying the biosynthesis of melatonin and its isomer in mulberry. Frontiers in Plant Science. 2021;12:708752.
105. Zheng X, Tan DX, Allan AC, Zuo B, Zhao Y, Reiter RJ, et al. Chloroplastic biosynthesis of melatonin and its involvement in protection of plants from salt stress. Scientific Reports. 2017;7(1):41236.
106. Zhu X, Liao J, Xia X, Xiong F, Li Y, Shen J, et al. Physiological and iTRAQ-based proteomic analyses reveal the function of exogenous γ-aminobutyric acid (GABA) in improving tea plant (Camellia sinensis L.) tolerance to cold temperature. BMC Plant Biology. 2019;19(1):43.
107. Ahammed GJ, Li X, Liu A, Chen S. Brassinosteroids in plant tolerance to abiotic stress. J Plant Growth Regul. 2020;39(4):1451-1464.
108. Byeon Y, Lee HY, Hwang OJ, Lee HJ, Lee K, Back K. Coordinated regulation of melatonin synthesis and degradation genes in Arabidopsis. J Pineal Res. 2014;56(3):272-279.
109. Tretyn A, Kendrick RE. Cytokinin metabolism and action in plants. Plant Growth Regul. 1992;11:1-10.
110. Li L, Ji G, Ye C, Shuai J, Zhao Y, Jiao Y, et al. PlantOrDB: A genome-wide ortholog database for land plants and green algae. BMC Plant Biol. 2015;15:161.