ANTAGONISM OF RESPONSES TO ARGININE VASOTOCIN BY ITS STRUCTURAL ANALOGS IN THE BULLFROG, RANA-CATESBEIANA

Antagonism of arginine vasotocin (AVT) actions in vivo by synthetic AVT analogs was studied in bullfrogs. In addition, one analog was examined for its in vitro effect on water flux in the urinary bladder and on vascular contraction in a dorsal aortic preparation. AVT and its analogs were injected into conscious bullfrogs while blood pressure and urine flow rate were recorded simultaneously. d(CH2)5Tyr(Me)AVT induced a slight, but not statistically significant, antidiuresis and a clear vasopressor response. d(CH2)5Tyr(Et)OVT and d(Et2)Tyr(Et)OVT did not show any intrinsic effects. These analogs partially blocked the antidiuretic effects of AVT and completely blocked the pressor effects of AVT. In studies in vitro, 1 μM d(Et2)Tyr(Et)OVT antagonized AVT-stimulated water flux, whereas 10 nM competitively inhibited (by about 50%) the vasocontraction induced by AVT. These results suggest that d(Et2)Tyr(Et)OVT has no intrinsic activity but retains a relatively high receptor affinity, thereby producing effective antagonism of AVT in target cells of vascular smooth muscle. On the other hand, this antagonist showed no detectable intrinsic activity and appeared to be a weaker antagonist in target cells of the urinary bladder. This suggests that there might be two types of AVT receptors in bullfrogs. © 1990.