R(+)-methanandamide inhibits tracheal response to endogenously released acetylcholine via capsazepine-sensitive receptors

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• 作者：Nieri ; Paola ; Martinotti ; Enrica ; Testai ; Lara ; Adinolfi ; Barbara ; Calderone ; Vincenzo ; Breschi ; Maria Cristina
• 关键词：Cannabinoid ; Vanilloid ; Cholinergic ; (Guinea-pig) ; Trachea
• 刊名：European Journal of Pharmacology
• 出版年：2003
• 出版时间：January 10, 2003
• 年：2003
• 卷：459
• 期：1
• 页码：75-81
• 全文大小：244 K

文摘

The effects of cannabinoid drugs on the cholinergic response evoked by electrical field stimulation (0.2 ms pulse width, 20 V amplitude, 10 Hz, 7.5 s train duration) in guinea-pig tracheal preparations were investigated. The stable analogue of the endocannabinoid anandamide, R(+)-methanandamide (10⁻⁷–10⁻⁴ M), produced a dose-dependent inhibition (up to 27±5 % of control) of electrical field stimulation-mediated atropine-sensitive response. This effect was not blocked by the selective cannabinoid CB₁ receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide hydrochloride (SR 141716A; 10⁻⁶ M), and was not reproduced with the cannabinoid CB₁/CB₂ receptor agonist R(+)-[2,3-dihydro-5-methyl-[(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate) (WIN 55,212-2; 10⁻⁸–10⁻⁵ M) or the cannabinoid CB₂ receptor selective agonist 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015; 10⁻⁸–10⁻⁵ M); it was, on the contrary, antagonized by the vanilloid antagonist 2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-2 benzazepine (capsazepine; 10⁻⁶ M). At the postjunctional level, neither R(+)-methanandamide nor WIN 55,212-2 nor JWH-015 did affect tracheal contractions induced by exogenous acetylcholine (10⁻⁶ M). An inhibitory vanilloid receptor-mediated effect on the cholinergic response evoked by electrical stimulation was confirmed with the vanilloid agonist capsaicin, at doses (3–6×10⁻⁸ M) which poorly influenced the basal smooth muscle tone of trachea. In conclusion, our data indicate that in guinea-pig trachea (a) neither CB₁ nor CB₂ cannabinoid receptor-mediated modulation of acetylcholine release occurs; (b) vanilloid VR1-like receptors appear involved in R(+)-methanandamide inhibitory activity on the cholinergic response to electrical field stimulation.