Alteration of cyclic amp-mediated hormonal responsiveness by bile acids in
cells of non-hepatic origin.
Bouscarel, Bernard, Susan Ceryak, Thomas W. Gettys, Hans Fromm, and Frances
Noonan.
Division of Gastroenterology and Nutrition, Department of Medicine, The
George Washington University Medical Center, Washington, DC 20037,Division of
Gastroenterology, Department of Medicine, Medical University of South
Carolina, Charleston, SC, Department of Dermatology, The George Washington
University Medical Center, Washington, DC 20037
APStracts 2:0006G, 1995.
The present study was undertaken to determine whether bile acids could inhibit
hormone-induced cAMP production in cells of non-hepatic origin, as previously
reported in the liver (Bouscarel et al. Am. J.Physiol. In press). The bile
acids, ursodeoxycholic acid (UDCA), chenodeoxycholic acid and deoxycholic
acid inhibited prostaglandin E1 (PGE1)- and isoproterenol-induced cAMP
production by 40% to 60%, in human skin fibroblasts and human umbilical vein
endothelial cells, respectively, to a similar extent as that observed in the
liver. However, in both models, the taurine conjugates of these respective
dihydroxy bile acids were without effect. Following permeabilization of
fibroblasts with saponin, UDCA and its taurine conjugates inhibited hormone
-induced cAMP production in a similar manner with a maximum inhibition of
around 55%. The other taurine conjugated dihydroxy bile acids were also able
to inhibit PGE1-induced cAMP production. Furthermore, in human fibroblasts,
UDCA was taken up in a dose and time-dependent manner, while there was no
uptake of taurocholic acid, even after 30 min incubation. Therefore, these
results suggest that plasma membrane crossing of bile acids is a requirement
for their inhibition of hormone-induced cAMP production. The ability of
certain bile acids to affect hormone-induced cAMP production in extrahepatic
tissues may be of pathophysiological significance in certain cholestatic
liver diseases.
Received 23 September 1994; accepted in final form 13 January 1995.
APS Manuscript Number G408-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.