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Abstract

Bile salt uptake by hepatocytes is modulated in part by changes in intracellular cyclic AMP. We studied the effect of activation of protein kinase C on cyclic AMP-mediated taurocholate uptake in isolated rat hepatocytes. Both dibutyryl cyclic AMP (2 × 10−6 mol/L) and glucagon (10−6 mol/L), which increase intracellular cyclic AMP, enhanced the initial uptake rate of taurocholate into hepatocytes, with maximal increases of 45% to 50% over the basal uptake rate. Vasopressin (10−9 mol/L), a hormone known to activate protein kinase C, and phorbol-12, 13-dibutyrate (10−5 mol/L) significantly inhibited the glucagon-stimulated increase in taurocholate uptake rate (72% ± 10% and 105% ± 13% inhibition, respectively). Basal (unstimulated) taurocholate uptake rate was not affected by vasopressin or phorbol-12, 13-dibutyrate. Down-regulation of the glucagon-stimulated transport was rapid and persisted during the 20-min experimental period. Angiotensin II had a similar but more transient inhibitory effect. Vasopressin and phorbol-12, 13-dibutyrate suppression of glucagon-stimulated taurocholate uptake rate was not accompanied by diminished cyclic AMP levels. Moreover, vasopressin and phorbol-12, 13-dibutyrate inhibited dibutyryl cyclic AMP-stimulated taurocholate uptake rate can be dissociated from alterations in the cyclic AMP levels. (Hepatology 1994;20:159–165.)