AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 2 300-G310, Copyright © 1995 by American Physiological Society

ARTICLES

Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC

B. Bouscarel, T. W. Gettys, H. Fromm and H. Dubner
Department of Medicine, George Washington University Medical Center, Washington, District of Columbia 20037.

The effect of bile acids on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis was investigated in isolated hamster hepatocytes. Bile acids had no direct effect on cAMP production. However, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid inhibited, by approximately 45%, cAMP formation induced by concentrations of glucagon greater than 1 nM, with a respective half-maximum inhibitory effect observed at 4 +/- 2 microM. Similar inhibition was observed with phorbol 12-myristate 13-acetate (PMA). Chenodeoxycholic, murocholic, and taurodeoxycholic acids were the next most potent bile acids. Taurolithocholic acid was 100-fold less potent than UDCA, whereas both ursocholic and taurocholic acids had no effect at concentrations up to 0.5 mM. Neither bile acids nor PMA affected either the binding of glucagon to its receptor, the cAMP-dependent phosphodiesterase, adenylate cyclase, or the inhibitory and stimulatory (Gs) GTP-binding proteins. The inhibitory effect of PMA and UDCA on glucagon-induced cAMP synthesis was abolished in the presence of the protein kinase C (PKC) inhibitor, staurosporine. Furthermore, UDCA induced PKC translocation from cytosol to membrane and stimulated phosphorylation of an 80-kDa protein substrate for PKC. In conclusion, mediated by PKC activation, bile acids inhibit glucagon-induced cAMP synthesis by uncoupling the glucagon receptor and Gs.

This article has been cited by other articles:

				C. Everett-Grueter, D. S. Edgerton, E. P. Donahue, S. Vaughan, C. A. Chu, D. K. Sindelar, and A. D. Cherrington The effect of an acute elevation of NEFA concentrations on glucagon-stimulated hepatic glucose output Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E449 - E459. [Abstract] [Full Text] [PDF]

				J. P. Meng, S. Ceryak, Z. Aratsu, L. Jones, L. Epstein, and B. Bouscarel Biphasic regulation by bile acids of dermal fibroblast proliferation through regulation of cAMP production and COX-2 expression level Am J Physiol Cell Physiol, September 1, 2006; 291(3): C546 - C554. [Abstract] [Full Text] [PDF]

				M. Le, L. Krilov, J. Meng, K. Chapin-Kennedy, S. Ceryak, and B. Bouscarel Bile acids stimulate PKC{alpha} autophosphorylation and activation: role in the attenuation of prostaglandin E1-induced cAMP production in human dermal fibroblasts Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G275 - G287. [Abstract] [Full Text] [PDF]

				N. Chignard, M. Mergey, D. Veissiere, R. Poupon, J. Capeau, R. Parc, A. Paul, and C. Housset Bile salts potentiate adenylyl cyclase activity and cAMP-regulated secretion in human gallbladder epithelium Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G205 - G212. [Abstract] [Full Text] [PDF]

				T. Niwa, Y. Nimura, and I. Niki Lack of effect of incretin hormones on insulin release from pancreatic islets in the bile duct-ligated rats Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E59 - E64. [Abstract] [Full Text] [PDF]

				B. Bouscarel, Y. Matsuzaki, M. Le, T. W. Gettys, and H. Fromm Changes in G protein expression account for impaired modulation of hepatic cAMP formation after BDL Am J Physiol Gastrointest Liver Physiol, June 1, 1998; 274(6): G1151 - G1159. [Abstract] [Full Text] [PDF]