VASOPRESSIN AND PHORBOL-12,13-DIBUTYRATE INHIBIT GLUCAGON OR CYCLIC AMP-STIMULATED TAUROCHOLATE UPTAKE IN ISOLATED RAT HEPATOCYTES

Bile salt uptake by hepatocytes is modulated in part by changes in int racellular cyclic AMP. We studied the effect of activation of protein kinase C on cyclic AMP-mediated taurocholate uptake in isolated rat he patocytes. Both dibutyryl cyclic AMP (2 x 10(-6) mol/L) and glucagon ( 10(-6) mol/L), which increase intracellular cyclic AMP, enhanced the i nitial uptake rate of taurocholate into hepatocytes, with maximal incr eases of 45% to 50% over the basal uptake rate. Vasopressin (10(-9) mo l/L), a hormone known to activate protein kinase C, and phorbol-12,13- dibutyrate (10(-5) moI/L) significantly inhibited the glucagon-stimula ted increase in taurocholate uptake rate (72% +/- 10% and 105% +/- 13% inhibition, respectively). Basal (unstimulated) taurocholate uptake r ate was not affected by vasopressin or phorbol-12,13 dibutyrate. Down- regulation of the glucagon-stimulated transport was rapid and persiste d during the 20-min experimental period. Angiotensin II had a similar but more transient inhibitory effect. Vasopressin and phorbol-12,13-di butyrate suppression of glucagon-stimulated taurocholate uptake rate w as not accompanied by diminished cyclic AMP levels. Moreover, vasopres sin and phorbol-12,13-dibutyrate inhibited dibutyryl cyclic AMP-stimul ated taurocholate uptake rate can be dissociated from alterations in t he cyclic AMP levels.