Different cellular mechanisms of vasopressin receptor V1 and V2 subtype in vasopressin-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 Ca(2+)-dependent PGE2 synthesis, whereas V2 receptor may stimulate it directly.
Takeuchi
K
K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yanai
N
N
Takahashi
N
N
Abe
T
T
Tsutsumi
E
E
Obinata
M
M
Abe
K
K
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D017483:Receptors, Vasopressin / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D000952:Antigens, Polyomavirus Transforming; D001552:Benzazepines; D010880:Piperidines; D015363:Quinolones; D017483:Receptors, Vasopressin; D014667:Vasopressins; C068644:OPC 21268; C076251:mozavaptan; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin