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Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation.
Eur J Pharmacol. 2014 Dec 15; 745:129-34.EJ

Abstract

We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3-30 mM) induced gastric relaxation which was not affected by 5-benzyloxytryptamine, a TRPM8 receptor antagonist, HC030031, a TRPA1 channel blocker. In addition, allylisothiocyanate, a TRPA1 agonist, but not (2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide, a selective TRPM8 agonist, induced gastric relaxation. Genic expression of TRPA1, but not of TRPM8, was revealed in mouse stomach. Indeed, menthol-induced gastric relaxation was significantly reduced by hexamethonium, cholinergic nicotinic receptor antagonist. Menthol, at concentrations that failed to affect gastric tone, reduced the contraction induced by dimethylphenylpiperazinium, nicotinic receptor agonist. The joint application of hexamethonium and atropine, muscarinc receptor antagonist, or hexamethonium and phentholamine, α-adrenergic receptor antagonist, did not produce any additive reduction of the relaxant response to menthol. Lastly, ondansetron, a 5-HT3 receptor antagonist, was ineffective. In conclusion, our study suggests that nicotinic receptors, but not TRP and 5-HT3 receptors, are molecular targets for menthol inducing murine gastric relaxation, ultimately due to the reduction of acetylcholine release from enteric nerves.

Authors+Show Affiliations

Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90128 Palermo, Italy. Electronic address: antonella.amato@unipa.it.Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90128 Palermo, Italy.Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90128 Palermo, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25446932

Citation

Amato, Antonella, et al. "Involvement of Cholinergic Nicotinic Receptors in the Menthol-induced Gastric Relaxation." European Journal of Pharmacology, vol. 745, 2014, pp. 129-34.
Amato A, Serio R, Mulè F. Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation. Eur J Pharmacol. 2014;745:129-34.
Amato, A., Serio, R., & Mulè, F. (2014). Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation. European Journal of Pharmacology, 745, 129-34. https://doi.org/10.1016/j.ejphar.2014.10.012
Amato A, Serio R, Mulè F. Involvement of Cholinergic Nicotinic Receptors in the Menthol-induced Gastric Relaxation. Eur J Pharmacol. 2014 Dec 15;745:129-34. PubMed PMID: 25446932.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation. AU - Amato,Antonella, AU - Serio,Rosa, AU - Mulè,Flavia, Y1 - 2014/10/16/ PY - 2014/07/10/received PY - 2014/09/16/revised PY - 2014/10/05/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/8/25/medline KW - Gastric relaxation KW - Menthol KW - Menthol (PubChem CID: 16666) KW - Nicotinic receptors KW - TRPA1 KW - TRPM8 SP - 129 EP - 34 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 745 N2 - We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3-30 mM) induced gastric relaxation which was not affected by 5-benzyloxytryptamine, a TRPM8 receptor antagonist, HC030031, a TRPA1 channel blocker. In addition, allylisothiocyanate, a TRPA1 agonist, but not (2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide, a selective TRPM8 agonist, induced gastric relaxation. Genic expression of TRPA1, but not of TRPM8, was revealed in mouse stomach. Indeed, menthol-induced gastric relaxation was significantly reduced by hexamethonium, cholinergic nicotinic receptor antagonist. Menthol, at concentrations that failed to affect gastric tone, reduced the contraction induced by dimethylphenylpiperazinium, nicotinic receptor agonist. The joint application of hexamethonium and atropine, muscarinc receptor antagonist, or hexamethonium and phentholamine, α-adrenergic receptor antagonist, did not produce any additive reduction of the relaxant response to menthol. Lastly, ondansetron, a 5-HT3 receptor antagonist, was ineffective. In conclusion, our study suggests that nicotinic receptors, but not TRP and 5-HT3 receptors, are molecular targets for menthol inducing murine gastric relaxation, ultimately due to the reduction of acetylcholine release from enteric nerves. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25446932/Involvement_of_cholinergic_nicotinic_receptors_in_the_menthol_induced_gastric_relaxation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00719-5 DB - PRIME DP - Unbound Medicine ER -