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
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.