POTENTIATION OF RECEPTOR-MEDIATED CAMP PRODUCTION - ROLE IN THE CROSS-TALK BETWEEN VASOPRESSIN V-1A AND V-2 RECEPTOR TRANSDUCTION PATHWAYS

Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transf ected with the V-1a and V-2 vasopressin receptors. Cell lines expressi ng V-1a, V-2, or both V-1a and V-2 receptors, were established and cha racterized. Stimulation of V-2 receptors by vasopressin induced a dose -dependent increase in cAMP accumulation, whereas stimulation of V-1a receptor resulted in an increase in intracellular calcium without any change in basal cAMP. The simultaneous stimulation of V-2 and V-1a rec eptors by vasopressin elicited an intracellular cAMP accumulation whic h was twice that induced by stimulation of V-2 receptor alone with dea mino-[D-Arg(8)]vasopressin. This potentiation between V-1a and V-2 rec eptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleim ide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying t hat an alteration in cAMP hydrolysis was not involved. Vasopressin, as well as PMA, had no effect on the forskolin-induced cAMP accumulation , suggesting that PKC did not directly stimulate the cyclase activity. On the other hand, vasopressin, like PMA, potentiated the cAMP accumu lation induced by cholera toxin, an activator of G alpha(s) protein. T hese results suggest that, in CHO cells, vasopressin V-1a receptor pot entiates the cAMP accumulation induced by the V-2 receptor through a P KC-dependent increase in the coupling between Gs protein and adenylyl cyclase.