Mechanisms of lithium-vasopressin interaction in rabbit cortical collecting tubule.

In single cortical collecting tubules (CCT) of the rabbit, guanosine 5'-triphosphate (GTP) increased the arginine vasopressin (AVP)-stimulated adenylate cyclase (AC) by 60% (P less than 0.05). In contrast, guanosine 5' O-(2-thio)-diphosphate (GDP-beta S), a competitive inhibitor of GTP action on the stimulatory guanine regulatory protein (Ns), reduced the AVP-stimulated AC activity by 72% (P less than 0.001), indicating the presence of endogenous GTP in the cells under study. That inhibitory effect was reversed by the addition of GTP to the incubation medium. In isolated perfused CCT, cholera toxin (CT) induced a significant increase in water permeability in the absence of AVP. In contrast, Bordetella pertussis toxin (BPT) did not modify the low AVP-independent water permeability. Lithium, an inhibitor of the hydrosmotic action of AVP, also inhibits the hydrosmotic action of CT by 70% (P less than 0.05) but not that of forskolin. The conclusions of the present study are Ns is required for AVP stimulation of AC in the CCT; Ns is functionally active in this system as evidenced by the hydrosmotic effect of CT; the lack of effect of BPT suggests that the low AVP-independent water permeability in the CCT is not the result of a tonic inhibition of the AC operating through the inhibitory guanine nucleotide regulatory protein; and the inhibition by lithium of the hydrosmotic action of AVP in the CCT appears to involve an interaction with the regulatory proteins (probably Ns) or with their binding to the catalytic unit of AC.