Cyclic gmp stimulates bile acid independent bile formation and
biliary bicarbonate excretion.
Myers, Nathaniel C., Stefan Gr[umlaut]une, Holly L. Jameson, and M.
Sawkat Anwer.
Departments of Veterinary Medicine and Pharmacology, Tufts
University School of Veterinary Medicine, North Grafton, MA
APStracts 2:0248G, 1995.
The effect of cGMP on hepatic bile formation was studied in isolated
perfused rat livers and rat hepatocytes. Studies in isolated perfused
rat livers showed that infusion of 8Br-cGMP (3 [mu]mol/min or 100
[mu]M) 1) increased bile flow without affecting biliary excretion of
simultaneously infused taurocholate, 2) increased biliary
concentration and excretion of HCO3-, but did not affect biliary
excretion of glutathione, and 3) increased net perfusate H+-efflux
without affecting hepatic O2-uptake. Studies in isolated rat
hepatocytes showed that 1) 8Br-cGMP increased intracellular pH in the
presence (but not in the absence of extracellular HCO3-), an effect
inhibited by DIDS and Na+ replacement, 2) 8Br-cGMP did not affect
taurocholate uptake and intracellular [Ca++], and 3) bile acids, like
ursodeoxycholate and cholate, did not increase cellular cGMP. Taken
together, these results indicate that cGMP stimulates bile acid
-independent bile formation, in part, by stimulating biliary HCO3-
excretion. cGMP may increase HCO3- excretion by stimulating
sinusoidal Na+-HCO3- cotransport, but not Na+/H+ exchange. cGMP,
unlike cAMP, may not regulate hepatic taurocholate transport, and
bile acid-induced HCO3--rich choleresis may not be mediated via cGMP.
Received 8 May 1995; accepted in final form 10 September 1995.
APS Manuscript Number G193-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95