Nelson D K, Glasbrenner B, Dahmen G, Riepl R L, Malfertheiner P, Adler G
Genesee Hospital, University of Rochester, New York 14607, USA.
Am J Physiol. 1996 Nov;271(5 Pt 1):G824-30. doi: 10.1152/ajpgi.1996.271.5.G824.
The contribution of muscarinic receptor subtypes to biliary control mechanisms is unclear. We investigated stimulated gallbladder function and release of associated hormones during M1-receptor blockade. Following a double-blind, randomized, crossover protocol, healthy volunteers each received placebo and telenzepine, a selective M1-receptor antagonist, as 2-h background infusion. Gallbladder contraction (by ultrasonography), bilirubin output, and release of cholecystokinin (CCK) and pancreatic polypeptide (PP) were assessed during increasing doses of endogenous (intraduodenal nutrient) and exogenous (hormonal) stimulation. All parameters were stimulated in a dose-dependent manner on placebo days. Contractile and secretory responses to low-dose caerulein (CCK analogue) were inhibited by 60-80% under telezepine, whereas high-dose (supraphysiological) stimulation overrode this effect. Similar inhibition was achieved during nutrient stimulation. CCK plasma levels rose during endogenous and exogenous stimulation but were unaffected by M1 blockade, whereas stimulated PP release was completely inhibited (> 100% decrease), reflecting suppressed vagal tone. Selective M1-receptor blockade inhibits the physiological response of the gallbladder in humans; this effect cannot be attributed to suppressed CCK release. Our findings support the hypothesis that CCK acts at the gallbladder via cholinergic nerves under physiological conditions. Viewed with our previous observations, nonselective antagonism of biliary function by atropine is primarily mediated through M1 muscarinic pathways.
毒蕈碱受体亚型对胆汁控制机制的作用尚不清楚。我们研究了M1受体阻断期间刺激的胆囊功能及相关激素的释放。按照双盲、随机、交叉方案，健康志愿者分别接受安慰剂和选择性M1受体拮抗剂替仑西平作为2小时的背景输注。在增加内源性（十二指肠内营养物）和外源性（激素）刺激剂量的过程中，评估胆囊收缩（通过超声检查）、胆红素输出以及胆囊收缩素（CCK）和胰多肽（PP）的释放。在安慰剂日，所有参数均呈剂量依赖性受到刺激。在替仑西平作用下，对低剂量雨蛙素（CCK类似物）的收缩和分泌反应受到60 - 80%的抑制，而高剂量（超生理剂量）刺激则克服了这种作用。在营养刺激期间也实现了类似的抑制。内源性和外源性刺激期间CCK血浆水平升高，但不受M1阻断的影响，而刺激的PP释放则完全受到抑制（下降> 100%），反映出迷走神经张力受到抑制。选择性M1受体阻断抑制人类胆囊的生理反应；这种作用不能归因于CCK释放受到抑制。我们的研究结果支持以下假设：在生理条件下，CCK通过胆碱能神经作用于胆囊。结合我们之前的观察结果来看，阿托品对胆汁功能的非选择性拮抗作用主要通过M1毒蕈碱途径介导。
