Different Cellular Mechanisms of Vasopressin Receptor V1 and V2 Subtype in Vasopression-Induced Adenosine 3′,5′-Monophosphate Formation in an Immortalized Renal Tubule Cell Line, TKC2

Vasopressin (VP) stimulates adenosine 3′,5′-monophosphate (cAMP) formation in an immortalized renal tubule cell line, TKC2, which is derived from transgenic mouse harboring temperature-sensitive SV40 T-antigen gene. VP (10^-8 M)induced cAMP formation was significantly attenuated by either non-peptide vasopressin receptor V₁ or V₂ subtype antagonist, OPC-21268 (10^-8 and 10^-6 M) or OPC-31260 (10^-8 and 10^-6 M), respectively, and it was completely abolished by combination of both agents (10^-6 M). VP (10^-8 M) also induced an increase in cytosolic free Ca²⁺ and prostaglandin (PG) E₂ synthesis, both of which were significantly inhibited by OPC-21268 (10^-8 M), but not by OPC-31260 (10^-6 M). Either OPC-21268 (10^-8 M), depletion of extracellular Ca²⁺ or inhibition of cyclooxygenase attenuated both VP-induced PGE₂ synthesis and cAMP formation. In conclusion, both V₁ and V₂ receptors can stimulate cAMP formation. V₁ receptor, however, stimulates cAMP formation via Ca²⁺-dependent PGE₂ synthesis, whereas V₂ receptor may stimulate it directly.