M(1) MUSCARINIC MECHANISMS REGULATE INTESTINAL-PHASE GALLBLADDER PHYSIOLOGY IN HUMANS

Citation
Dk. Nelson et al., M(1) MUSCARINIC MECHANISMS REGULATE INTESTINAL-PHASE GALLBLADDER PHYSIOLOGY IN HUMANS, American journal of physiology: Gastrointestinal and liver physiology, 34(5), 1996, pp. 824-830
Citations number
35
Categorie Soggetti
Physiology
ISSN journal
01931857
Volume
34
Issue
5
Year of publication
1996
Pages
824 - 830
Database
ISI
SICI code
0193-1857(1996)34:5<824:MMMRIG>2.0.ZU;2-X
Abstract
The contribution of muscarinic receptor subtypes to biliary control me chanisms is unclear. We investigated stimulated gallbladder function a nd release of associated hormones during M(1)-receptor blockade. Follo wing a double-blind, randomized, crossover protocol, healthy volunteer s each received placebo and telenzepine, a selective M(1)-receptor ant agonist, as 2-h background infusion. Gallbladder contraction (by ultra sonography), bilirubin output, and release of cholecystokinin (CCK) an d pancreatic polypeptide (PP) were assessed during increasing doses of endogenous (intraduodenal nutrient) and exogenous (hormonal) stimulat ion. All parameters were stimulated in a dose-dependent manner on plac ebo days. Contractile and secretory responses to low-dose caerulein (C CK analogue) were inhibited by 60-80% under telenzepine, whereas high- dose (supraphysiological) stimulation overrode this effect. Similar in hibition was achieved during nutrient stimulation. CCK plasma levels r ose during endogenous and exogenous stimulation but were unaffected by M(1) blockade, whereas stimulated PP release was completely inhibited (> 100% decrease), reflecting suppressed vagal tone. Selective M(1)-r eceptor blockade inhibits the physiological response of the gallbladde r in humans; this effect cannot be attributed to suppressed CCK releas e. Our findings support the hypothesis that CCK acts at the gallbladde r via cholinergic nerves under physiological conditions. Viewed with o ur previous observations, nonselective antagonism of biliary function by atropine is primarily mediated through M(1) muscarinic pathways.