DESENSITIZATION OF VASOPRESSIN SENSITIVE ADENYLATE-CYCLASE BY VASOPRESSIN AND PHORBOL ESTERS

Desensitization of vasopressin V2 receptor-mediated adenylate cyclase was studied in canine kidney cell line, MDCK cells. Overnight treatment of MDCK cells with arginine vasopressin (AVP) resulted in a loss of vasopressin receptors and an inhibition of cAMP accumulation in response to AVP. Both the loss of receptor and reduction in cAMP accumulation werer time- and AVP concentration-dependent. Desensitization was selective for AVP because cAMP formation in response to isopreterenol, prostaglandin E1 (PGE1) and forskolin was not affected by AVP pre-treatment. Pre-treatment of MDCK cells with phorbol dibutyrate (PDBu) also caused a dose-dependent inhibition of AVP mediated cAMP accumulation, but not of isoproterenol-, PGE1- and forskolin-induced cAMP accumulation. PDBu pre-treatment did not cause loss of vasopressin receptors. Insteasd, the affinity for vassopressin was changed by PDBu treatment. Pre-treatment of the cells with pertussis toxin (PT) had no effect on the desensitization and ownregulation of vasopressin (V2) receptors, suggesting that the desensitization of AVP-mediated cAMP accumulation and that downregulation of V2 receptors required agonist occupanyc of the receptors, whereas the affinity of the receptors was changed by phorbol ester treatment. © 1990.