AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 2 243-G251, Copyright © 1993 by American Physiological Society

ARTICLES

Ursodeoxycholate mobilizes intracellular Ca2+ and activates phosphorylase a in isolated hepatocytes

B. Bouscarel, H. Fromm and R. Nussbaum
Department of Medicine, George Washington University Medical Center, Washington, District of Columbia 20037.

In isolated hamster hepatocytes, ursodeoxycholic acid (UDCA) mobilized intracellular free calcium ([Ca2+]i) and activated phosphorylase a with a half-maximally effective concentration of 188 and 9 microM, respectively. Addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) did not affect the maximum [Ca2+]i mobilized by UDCA; however, [Ca2+]i returned to basal levels in 4-5 min compared with > 10 min in the absence of EGTA. Both UDCA and vasopressin activated phosphorylase a to the same extent in the presence and absence of extracellular Ca2+, and the effect of both agents was abolished when the cells were depleted in Ca2+. Vasopressin (100 nM) did not further mobilize [Ca2+]i or activate phosphorylase a when combined with 500 microM UDCA. However, unlike vasopressin, UDCA did not stimulate inositol 1,4,5-trisphosphate (IP3) formation. In contrast to taurine-conjugated UDCA (TUDCA), concentration < or = 500 microM of glycine-conjugated UDCA (GUDCA) did not affect either [Ca2+]i or phosphorylase a. Lithocholic acid and taurolithocholic acid (TLCA) displayed the highest affinity for Ca2+. In addition, TLCA, chenodeoxycholic acid, and NaF stimulated Ca2+ efflux at concentrations as low as 100 microM, 200 microM, and 5 mM, respectively. Conversely, UDCA, TUDCA, and GUDCA presented the lowest affinity for Ca2+ and had no effect on Ca2+ efflux. The 28% increase in Ca2+ release induced by TLCA alone was further augmented to approximately 60% when TLCA was combined with UDCA, TUDCA, or GUDCA. However, Ca2+ efflux induced by NaF was not further increased by UDCA and its conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				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]

				P Milkiewicz, M G Roma, E Elias, and R Coleman Hepatoprotection with tauroursodeoxycholate and {beta} muricholate against taurolithocholate induced cholestasis: involvement of signal transduction pathways Gut, July 1, 2002; 51(1): 113 - 119. [Abstract] [Full Text] [PDF]

				T. Miura, R. Ouchida, N. Yoshikawa, K. Okamoto, Y. Makino, T. Nakamura, C. Morimoto, I. Makino, and H. Tanaka Functional Modulation of the Glucocorticoid Receptor and Suppression of NF-kappa B-dependent Transcription by Ursodeoxycholic Acid J. Biol. Chem., December 7, 2001; 276(50): 47371 - 47378. [Abstract] [Full Text] [PDF]

				E. R. Kokoska, G. S. Smith, A. B. Wolff, Y. Deshpande, C. L. Rieckenberg, A. Banan, and T. A. Miller Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells Am J Physiol Gastrointest Liver Physiol, August 1, 1998; 275(2): G322 - G330. [Abstract] [Full Text] [PDF]