Mast cells and the biogenic amine, histamine, play a central role in inflammatory reactions. Nerve growth factor (NGF) is essetial for the survival of neurones and has significant role in inflammation and repair of tissues. It has been shown, that NGF induces degranulation of mast cells by interacting with tropomyosine-receptor kinase A (TrkA receptor). NGF can induce release of histamine and other mediators from mast cells or enhance secretion induced by different stimuli. The results of our and others previous studies show, that histamine release from mast cells induced by NGF is strongly dependent on the concentration of extracellular Na+ , Ca2+ ions. The extracellular Na+ ions can affect the activity of Na+ /Ca2+ exchanger of mast cells. Na+ , Ca2+ exchange mechanisms could be important in secretory process of mast cells. The studies of different signaling molecules in NGF induced histamine relese have shown that tyrosine kinase, phosphatidylinositol-3-kinase, protein kinase C and phospholipase C are also involved in the signal transduction process responsible for NGF induced histamine secretion from mast cells. These data indicate that NGF may contribute in allergic reactions and many other inflammatory states. Advances in Clinical Toxicology ISSN: 2577-4328 MEDWIN PUBLISHERS Committed to Create Value for Researchers Mechanism of Action of Nerve Growth Factor Induced Histamine Release from Mast Cells during the Inflammation Process Adv Clin Toxicol Mechanism of Action of Nerve Growth Factor Induced Histamine Release from Mast Cells during the Inflammation Process Ferjan I* Institute of Pharmacology and Experimental Toxicology, Medical faculty of Ljubljana, Slovenia *Corresponding author: Ilonka Ferjan, Institute of Pharmacology and Experimental Toxicology, Medical faculty of Ljubljana, Korytkova ulica 2, 1000, Ljubljana, Slovenia, Email: ilonka.ferjan@mf.uni-lj.si Review Article Volume 8 Issue 1 Received Date: December 12, 2022 Published Date: January 23, 2023 DOI: 10.23880/act-16000255 Abstract Mast cells and the biogenic amine, histamine, play a central role in inflammatory reactions. Nerve growth factor (NGF) is essetial for the survival of neurones and has significant role in inflammation and repair of tissues. It has been shown, that NGF induces degranulation of mast cells by interacting with tropomyosine-receptor kinase A (TrkA receptor). NGF can induce release of histamine and other mediators from mast cells or enhance secretion induced by different stimuli. The results of our and others previous studies show, that histamine release from mast cells induced by NGF is strongly dependent on the concentration of extracellular Na +, Ca2+ ions. The extracellular Na + ions can affect the activity of Na +/Ca2+ exchanger of mast cells. Introduction In the inflammation process, mast cells have a very important role. After the activation of mast cells, they release many mediators involved in the inflammation [1]. Biogenic amine, histamine, is one of the essential inlammatory mediator [2]. Nerve growth factor (NGF) is essetial for the survival of neurones and has a signifficant role in inflammation and repair of tissues [3-5]. It has been shown, that the extracellular ionic composition influences the secretion process of mast cells [6]. The existence of Na+/Ca2+ exchanger on rat mast cell membrane has been demonstrated [7]. The action of Na +/ Ca2+ exchanger depends on the concentration of extracellular Na+ and Ca2+ ions. Mechanism of Action of Nerve Growth Factor Induced Histamine Release from Mast Cells during the Inflammation Process. Adv Clin Toxicol 2023, 8(1): 000255. Copyright© Ferjan I. ions and is enhanced with increasing concentration of Ca 2+ ions in the medium. However, lowering extracellular Na+ ions increases histamine release induced by NGF. In the medium containing low concentration of Ca 2+ ions, removal of Na+ ions from the medium further potentiates histamine release induced by NGF (6). The Involvement of Na+/Ca 2+ Exchanger in the Degranulation Process of Mast Cell On mast cell membrane Na +Ca2+ exchanger has been demonstrated [7]. The extracellular Na+ ions can affect the activity of Na +Ca2+ exchanger of mast cells. In physiological conditions the exchanger exchanges Ca 2+ ions from the cell for Na+ ions from the medium [9]. In the medium containing low concentrations of Na + ions, the reverse action of the exchanger can be activated, resulting in influx of Ca2+ ions from the medium into the cell [9]. The increased concentration of intracellular free Ca 2+ ions leads to enhanced histamine release. Inhibitor of Na+/Ca 2+ exchanger, amiloride, reduces the potentiated histamine release under these conditions [8]. These data indicate the importance of NGF in many states that are involved in mast cell activation. NGF may contribute in asthma and many other allergic reastions [11]. Conclusion • Histamine release induced by NGF is dependent on the presence of extracellular Na+ and Ca2+ ions [6,13]. • Extracellular Na + and Ca 2+ ions regulate the activity of Na+/Ca2+ exchanger of mast cells [7,8]. The influx of Ca 2+ ions from the medium into the cell leads to the increased concentration of intracellular free Ca 2+ ions which enhances histamine release from mast cells. Minnone G, Benedetti FD, Bracci-Laudiero L (2017) NGF and its receptors in the regulation of inflammatory response Int J Mol Sci 18(5): 1028. 11. Skaper SD (2017) Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology 151(1): 1-15. 12. Smith TF, Sanchez Legrand F, McKean LP , Kutner MH, Cragoe EJ, et al. (1992) Role of sodium in mediator Advances in Clinical Toxicology 3 Ferjan I. Mechanism of Action of Nerve Growth Factor Induced Histamine Release from Mast Cells during the Inflammation Process. Adv Clin Toxicol 2023, 8(1): 000255. Copyright© Ferjan I. release from human basophils. J Allergy Clin Immunol 89(5): 978-986. 13.