Oxytocin induced cAMP-dependent protein kinase activation and urokinase-type plasminogen activator production in LLC-PK1 renal epithelial cells is mediated by the vasopressin V2-receptor.

Using a variety of peptide analogues of oxytocin (OT) and Arg8-vasopressin (AVP), OT-mediated induction of urokinase-type plasminogen activator (uPA) was examined in LLC-PK1 renal epithelial cells, which possess distinct high-affinity receptors of both the OT- and vasopressin renal (V2-) types. OT or OT-receptor specific agonists induced concentration-dependent cAMP synthesis, activation of the cAMP-dependent protein kinase (cAMP-PK) and uPA production consistent with their respective binding affinities for the V2- and not the OT-receptor. OT-mediated uPA induction could be inhibited in a concentration-dependent fashion by coincubation with a V2/V1-receptor specific antagonist, but not by an OT-receptor specific antagonist. Results implied that stimulation of cAMP- and uPA responses in LLC-PK1 cells by OT was V2-receptor-mediated.