M1-muscarinic mechanisms regulate intestinal-phase gallbladder
physiology in man.
Nelson, Daniel K., Bernd Glasbrenner, Gudrun Dahmen, Rudolf L. Riepl,
Peter Malfertheiner, Guido Adler.
University of Ulm, Germany; The Genesee Hospital, University of
Rochester, New York; Medizinische Klinik Innenstadt, University of
Munich, Germany; University of Magdeburg, Germany
APStracts 3:0101G, 1996.
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 2h 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 telenzepine, while high-dose (supraphysiologic) 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, while stimulated PP
release was completely inhibited (>100% decrease), reflecting
suppressed vagal tone. Selective M1-receptor blockade inhibits the
physiologic response of the gallbladder in man; this effect cannot be
attributed to suppressed CCK release. Our findings support the
hypothesis that CCK acts at the gallbladder via cholinergic nerves
under physiologic conditions. Viewed with our previous observations,
nonselective antagonism of biliary function by atropine is primarily
mediated through M1-muscarinic pathways.
Received 24 July 1995; accepted in final form 30 April 1996.
APS Manuscript Number G310-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96