Potentiation of receptor-mediated cAMP production: role in the cross-talk between vasopressin V1a and V2 receptor transduction pathways Available to Purchase

Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transfected with the V_1a and V₂ vasopressin receptors. Cell lines expressing V_1a, V₂, or both V_1a and V₂ receptors, were established and characterized. Stimulation of V₂ 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 V₂ and V_1a receptors by vasopressin elicited an intracellular cAMP accumulation which was twice that induced by stimulation of V₂ receptor alone with deamino-[D-Arg⁸]vasopressin. This potentiation between V_1a and V₂ receptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleimide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying that 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 accumulation induced by cholera toxin, an activator of Gα_s protein. These results suggest that, in CHO cells, vasopressin V_1a receptor potentiates the cAMP accumulation induced by the V₂ receptor through a PKC-dependent increase in the coupling between Gs protein and adenylyl cyclase.