Stimulation of bile acid synthesis by dibutyryl cyclic AMP in isolated rat hepatocytes

G. S. Sundaram, Vicki Rothman, Simeon Margolis

Research output: Contribution to journalArticle

Abstract

Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55:45 in control cells to 41:59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.

Original languageEnglish (US)
Pages (from-to)443-447
Number of pages5
JournalLipids
Volume18
Issue number7
DOIs
StatePublished - Jul 1 1983

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

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