title: Prostaglandin E2 and cyclic AMP response to vasopressin in renal medullary tubular cells.
abstract: 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.
mesh_terms: 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
chemical_list: 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