Vasotocin-sensitive adenylate cyclase in frog glomeruli.
Adenylate cyclase sensitivity to neurohypophyseal hormones was investigated in isolated glomeruli and in nephron segments microdissected from collagenase-treated kidneys of Rana ridibunda. Vasotocin treatment increased adenylate cyclase activity in glomeruli and in collecting ducts and did not modify it in proximal convoluted tubules and in early and late distal tubules. In glomeruli, the hormonal stimulation resulted mainly in a decrease in the Km value for adenylate cyclase, which means a higher affinity for substrate (ATP) to the enzyme, whereas the response to forskolin was accounted for by increases both in affinity for substrate and in maximal adenylate cyclase velocity. The homologous neurohypophyseal hormones stimulated frog glomerular adenylate cyclase with the following rank order of affinities: hydrin 1 > or = AVT = AVP > or = hydrin 2 > OT > or = mesotocin > isotocin; structural analogs dDAVP, VDAVP, dVDAVP, and [Phe2,Orn8]VT had weak agonistic properties, [Thr4,Gly7]OT was inactive, and the antagonists OVTA, d(CH2)5Tyr(Et)2VAVP, and des-Gly9-d(CH2)5Tyr(Et)2VAVP inhibited hormone-induced enzyme activation with similar apparent inhibition constants. The vasotocin receptors triggering adenylate cyclase stimulation in frog glomeruli differ pharmacologically from V2 vasopressin receptors of mammalian kidneys and may also differ from V2-like vasotocin receptors of amphibian skin and urinary bladder.
Ammar
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Laboratoire de Physiologie Cellulaire, Collège de France, Paris.
Roseau
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S
Butlen
D
D
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D010909:Pituitary Hormones, Posterior / Q000494:pharmacology; D011895:Rana ridibunda; D014668:Vasotocin / Q000494:pharmacology*
D010909:Pituitary Hormones, Posterior; D015636:Magnesium Chloride; D001127:Arginine Vasopressin; D005576:Colforsin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D014668:Vasotocin