BACKGROUND & AIMS:
:Twitch contractions of the rabbit vas deferens elicited by electrical field stimulation were inhibited by tetrodotoxin, guanethidine, bretylium and alpha,beta-methylene-ATP but were unaffected by hexamethonium, physostigmine, 1,1-dimethyl-4-phenylpiperazinium and prazosin, suggesting that they resulted from ATP released following postganglionic sympathetic nerve stimulation. McN-A-343 inhibited but carbachol and several other muscarinic agonists potentiated the twitch contractions; these effects were not modified by hexamethonium or physostigmine. Muscarinic agonists had no effect on the tension in unstimulated organs whereas contractions elicited by ATP, noradrenaline and KCl were potentiated by carbachol but remained unaffected by McN-A-343. The responses of the twitch contractions to McN-A-343 and carbachol were inhibited to different degrees by antimuscarinic drugs: the affinity (pA2) of atropine, secoverine and himbacine against McN-A-343 and carbachol was similar. However, pirenzepine, telenzepine, trihexyphenidyl, dicyclomine and hexahydro-sila-difenidol displayed preferential antagonism of the responses to McN-A-343 whereas the converse was true for AF-DX 116 and gallamine. The highly significant correlation between the pA2 values obtained for 10 antagonists against carbachol responses in rabbit vas deferens and rat left atrium suggests that the receptors may be similar. The data support the presence of a presynaptic M1-receptor mediating inhibition and a postsynaptic, cardiac-like M2-receptor responsible for enhancing neurogenic contractions in rabbit vas deferens.
背景与目标:
: 电场刺激引起的兔输精管的抽搐收缩被河豚毒素,胍乙啶,bretylium和 α,β-亚甲基-ATP抑制,但不受六甲铵,毒扁豆碱,1,1-二甲基-4-苯基哌嗪和哌唑嗪的影响,表明它们是由神经节后交感神经刺激后释放的ATP引起的。McN-A-343抑制,但卡巴胆碱和其他几种毒蕈碱激动剂增强了抽搐收缩; 六甲铵或毒扁豆碱未改变这些作用。毒蕈碱激动剂对未刺激器官的张力没有影响,而由ATP,去甲肾上腺素和KCl引起的收缩被卡巴胆碱增强,但不受McN-A-343影响。抗毒蕈碱药物在不同程度上抑制了抽搐收缩对McN-A-343和卡巴胆碱的反应: 阿托品,赛科林和喜巴因对McN-A-343和卡巴胆碱的亲和力 (pA2) 相似。然而,哌仑西平,替仑西平,三己苯甲基,二环胺和六氢-sila-difenidol表现出对McN-A-343反应的优先拮抗作用,而AF-DX 116和没食子胺则相反。在兔输精管和大鼠左心房中,针对卡巴胆碱反应的10种拮抗剂获得的pA2值之间的高度显着相关性表明受体可能相似。数据支持存在突触前M1-receptor介导抑制和突触后,心脏样M2-receptor负责增强兔输精管的神经源性收缩。