Prostaglandin E2 and cyclic AMP response to vasopressin in renal medullary tubular cells.
Rat renal medullary tubular cells, prepared by collagenase dispersion and hypotonic lysis, were introduced in Teflon chambers for superfusion. Prostaglandin (PG) E2 and cyclic adenosine 5'-monophosphate (cAMP) production was measured in the effluent. Arginine vasopressin (AVP) but not 1-deamino-8-D-arginine vasopressin (dDAVP) (10(-10)-10(-6) M), induced a dose-dependent increase in PGE2 synthesis, whereas AVP and dDAVP produced a similar dose-dependent increase in cAMP synthesis. The Ca2+ ionophore A23187 (10(-6) M) stimulated PGE2 synthesis but not cAMP production. In contrast, forskolin (10(-5) M) stimulated cAMP synthesis without affecting PGE2 generation. The pressor antagonists dEt2AVP and d(CH2)5Tyr(Me)AVP (10(-5) M) completely inhibited the PGE2 response to 10(-8) M AVP, whereas d(CH2)5-D-LeuVAVP (10(-6) M), a mixed pressor-antidiuretic antagonist, inhibited incompletely. dEt2AVP did not significantly affect cAMP synthesis in response to 10(-8) M AVP, whereas d(CH2)5-D-LeuVAVP, and unexpectedly also d(CH2)5Tyr(Me)AVP, were inhibitory. dPTyr(Me)AVP (10(-7) M), a pressor antagonist, had an unexpectedly high cAMP-stimulating capacity. In Ca2+-free media containing EGTA, the PGE2 response to AVP and A23187 was inhibited. Nifedipine (10(-6) M) did not significantly inhibit the AVP-stimulated PGE2 production. Thus AVP-stimulated PGE2 synthesis is linked to a V1-receptor in renal medullary tubular cells and occurs independently to the activation of adenylate cyclase through a V2-receptor.
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D007679:Kidney Medulla; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000037:antagonists & inhibitors
D011458:Prostaglandins E; D014667:Vasopressins; D001127:Arginine Vasopressin; D005576:Colforsin; D000001:Calcimycin; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D009543:Nifedipine; D015232:Dinoprostone; D002118:Calcium