FROG GLOMERULAR VASOTOCIN RECEPTORS RESEMBLE MAMMALIAN V-1B RECEPTORS

Vasotocin receptors were investigated in glomeruli and nephron segment s microdissected from collagenase-treated kidneys of Rana ridibunda, u sing )Tyr(Me)(2),Thr(4),Orn(8),I-125-Tyr-NH29]vasotocin (I-125-OVTA) a s a radioligand. Specific I-125-OVTA binding sites were found only in glomeruli and not in all tubule segments tested. Glomerular receptors exhibited the following stereospecificity for recognition of vasotocin analogues: Tyr-NH29-LA-V-1a > I-125-OVTA > arginine vasotocin (AVT) g reater than or equal to [d(CH2)(5)Tyr(Me)(2)]AVP > OVTA greater than o r equal to [Phe(2),Orn(8)]VT > oxytocin (OT) greater than or equal to [d(CH2)(5)-Sar(7)]AVP > desGly(9)[d(CH2)(5)Tyr(Et)(2)]VAVP greater tha n or equal to [d(CH2)(5)Tyr(Et)(2)]VAVP AVP [1-desamino-8-D-arginine]v asopressin (DDAVP) > [Thr(4),Gly(7)]OT. In addition, vasotocin enhance d [H-3]inositol phosphate production in sieved glomeruli labeled with myo-[3H]inositol; the rank order of structural vasotocin analogues for stimulation of phosphoinositidase C was [Phe(2),Orn(8)]VT > AVT > OT > AVP > DDAVP, whereas [Thr(4),Gly(7)]OT was almost inactive, and the rank order of antagonists for inhibition of hormone-induced enzyme act ivation was Tyr-NH29-LA-V-1a > [d(CH2)(5)Tyr(Me)(2)]AVP = OVTA > [d(CH 2)(5)Sar(7)]AVP > [d(CH2)(5)Tyr(Et)(2)]VAVP greater than or equal to d esGly(9)[d(CH2)(5)Tyr(Et)(2)]VAVP. Results indicate that the I-125-OVT A-labeled binding sites detected in frog glomeruli reveal the pharmaco logical properties of mammalian V-1b-pituitary vasopressin receptors a nd might be physiological vasotocin receptors involved in phosphoinosi tidase C stimulation.