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

Am J Physiol. 1993 Feb;264(2 Pt 1):G243-51. doi: 10.1152/ajpgi.1993.264.2.G243.

Abstract

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)

Publication types

  • Comparative Study

MeSH terms

  • Aminoquinolines
  • Animals
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / pharmacology
  • Calcium / metabolism*
  • Cell Separation
  • Chelating Agents
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Intracellular Membranes / metabolism*
  • L-Lactate Dehydrogenase / metabolism
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Phosphorylase a / metabolism*
  • Phosphorylases / metabolism
  • Ursodeoxycholic Acid / pharmacology*
  • Vasopressins / pharmacology

Substances

  • Aminoquinolines
  • Bile Acids and Salts
  • Chelating Agents
  • Vasopressins
  • Ursodeoxycholic Acid
  • Quin2-acetoxymethyl ester
  • Inositol 1,4,5-Trisphosphate
  • L-Lactate Dehydrogenase
  • Phosphorylase a
  • Phosphorylases
  • Calcium