Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

The ability of d(CH₂)₅‐Tyr(Me)‐arginine‐8‐vasopressin, an antagonist of peripheral pressoric (V1‐type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, ³H‐arginine‐8‐vasopressin (AVP) specifically labels a single class of binding sites with a K_d of 2.9nM and maximum binding site concentration of 19.8 fmole/mg protein. ³H‐Antag also labels a single class of membrane sites but with higher affinity (K_d=0.47nM) and lower capacity (10.1 fmole/mg protein) than ³H‐AVP. The rank order of potency of various competitor peptides for ³H‐AVP and ³H‐Antag binding was similar. Oxytocin was 100–1,000 fold less potent than AVP in competing for binding with both ligands. ³H‐AVP and ³H‐Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin‐stimulated phosphatidylinositol hydrolysis in septal tissue slices.