VASOTOCIN-SENSITIVE ADENYLATE-CYCLASE IN FROG GLOMERULI

Adenylate cyclase sensitivity to neurohypophyseal hormones was investi gated in isolated glomeruli and in nephron segments microdissected fro m collagenase-treated kidneys of Rana ridibunda. Vasotocin treatment i ncreased adenylate cyclase activity in glomeruli and in collecting duc ts and did not modify it in proximal convoluted tubules and in early a nd late distal tubules. In glomeruli, the hormonal stimulation resulte d mainly in a decrease in the K-m value for adenylate cyclase, which m eans 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 homologou s neurohypophyseal hormones stimulated frog glomerular adenylate cycla se with the following rank order of affinities: hydrin 1 greater than or equal to AVT = AVP greater than or equal to hydrin 2 > OT greater t han or equal to mesotocin > isotocin; structural analogs dDAVP, VDAVP, dVDAVP, and [Phe(2),Om(8)]VT had weak agonistic properties, [Thr(4),G ly(7)]OT was inactive, and the antagonists OVTA, d(CH2)(5)Tyr(Et)(2)VA VP, and des-Gly(9)-d(CH3)(5)Tyr(Et)(2)VAVP inhibited hormone-induced e nzyme activation with similar apparent inhibition constants. The vasot ocin receptors triggering adenylate cyclase stimulation in frog glomer uli differ pharmacologically from V-2 vasopressin receptors of mammali an kidneys and may also differ from V-2-like vasotocin receptors of am phibian skin and urinary bladder. (c) 1995 Academic Press. Inc.