[3H]desGly-NH29-d(CH2)5[D-Ileu2,Ileu4]AVP: An AVP V2 receptor antagonist radioligand

Abstract Binding characteristics of the selective V 2 antagonist radioligand [ 3 H]desGly-NH 2 9 -d(CH 2 ) 5 [D-Ileu 2 ,Ileu 4 ]AVP to rat kidney were determined. Binding was specific, saturable and reversible. The peptide bound to a single class of high-affinity binding sites with B max 69.4±6.8 fmol/mg protein and K D 2.8±0.3 nM . AVP and other related peptides displaced [ 3 H]desGly-NH 2 9 -d(CH 2 ) 5 [D-Ileu 2 ,Ileu 4 ]AVP binding. The order of potency of inhibition was desamino-D-AVP > AVP > d(CH 2 ) 5 [D-Ileu 2 ,Ileu 4 ]AVP > oxytocin > d(CH 2 ) 3 [Tyr(Me) 2 ]AVP > d(CH 2 ) 5 [sarcosine 7 ]AVP, which is typical of a selective V 2 radioligand. Autoradiographic localization of [ 3 H]desGly-NH 2 9 -d(CH 2 ) 5 [D-Ileu 2 ,Ileu 4 ]AVP binding sites in kidney showed dense binding in the inner and outer medulla with less binding in the cortex, which is consistent with known renal V 2 receptor distribution.