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 K-m 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 greater than or equal to AVT = AVP greater than or equal to hydrin 2 > OT greater than or equal to mesotocin > isotocin; structural analogs dDAVP, VDAVP, dVDAVP, and [Phe(2),Om(8)]VT had weak agonistic properties, [Thr(4),Gly(7)]OT was inactive, and the antagonists OVTA, d(CH2)(5)Tyr(Et)(2)VAVP, and des-Gly(9)-d(CH3)(5)Tyr(Et)(2)VAVP inhibited hormone-induced enzyme activation with similar apparent inhibition constants. The vasotocin receptors triggering adenylate cyclase stimulation in frog glomeruli differ pharmacologically from V-2 vasopressin receptors of mammalian kidneys and may also differ from V-2-like vasotocin receptors of amphibian skin and urinary bladder. (c) 1995 Academic Press. Inc.