Functional characterization of acetylcholine receptors and calcium signaling in rat testicular capsule contraction

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• 作者：Edilson Dantas da Silva J¨²nior ; Bruno Palmieri de Souza ; Juliano Quintela Dantas Rodrigues ; Afonso Caricati-Neto ; Aron Jurkiewicz ; Neide Hyppolito Jurkiewicz
• 关键词：Cholinergic agonists ; Muscarinic acetylcholine receptors ; Calcium ; Rat testicular capsule.
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：714
• 期：1-3
• 页码：405-413
• 全文大小：777 K

文摘

The motor activity of mammalian testicular capsule (TC) contributes to male fertility and infertility, but the acetylcholine receptors related to the contractions induced by cholinergic drugs are poorly known. Indeed to characterize the acetylcholine receptors and cellular signaling by Ca²⁺ involved in TC motor activity of rats, the potency of agonists (pD₂) and antagonists (pA₂) of acetylcholine receptors, and effects of Ca²⁺ cellular transport blockers on the cholinergic contractions were evaluated. pD₂ values of acetylcholine (5.98) were ten-fold higher than that of carbachol (4.99). Efficacy (E_max) of acetylcholine and carbachol to induce contractions corresponded to 95 % and 97 % of E_max for KCl, but E_max for nicotine was very low (8 % of E_max for KCl). Further, physostigmine did not affect the acetylcholine potency. Contractions induced by acetylcholine or carbachol were antagonized by muscarinic but not nicotinic antagonist. The order of pA₂ values obtained for muscarinic antagonists, namely atropine>4-DAMP>AF-DX116>pirenzepine, corresponded to a typical profile of M₃ receptors. Contractions induced by acetylcholine or carbachol were inhibited by blockers of Ca²⁺ influx through voltage-dependent calcium channels (nifedipine and Ni²⁺), Ca²⁺ reuptake by sarco-endoplasmic reticulum (cyclopiazonic acid) and mitochondria (FCCP). The protein kinase C (PKC) inhibitor chelerythrine only affected the acetylcholine-induced contraction. These results suggest that TC motor activity of rats are mediated mainly by M₃ receptors followed by the increase of cytosolic Ca²⁺ concentration regulated by voltage-dependent calcium channels, sarco-endoplasmic reticulum and mitochondria. Furthermore, the differential effects of chelerythrine in the acetylcholine or carbachol-induced contractions are discussed.