[¹²⁵i]-[d(CH₂)₅, sar⁷] AVP: A selective radioligand for v₁ vasopressin receptors

Arginine⁸-vasopressin (AVP) acts on vascular and hepatic V₁ receptors to influence blood pressure and glycogenolysis respectively. We have radioiodinated the AVP V₁ receptor antagonist, [1-(βmercapto-βbeta;cyclopentamethylenepropionic-acid), 7-sarcosine, 8-arginine] vasopressin ([d(CH₂)₅, Sar⁷]AVP) and determined its receptor-binding properties in rat liver and kidney plasma membranes. The binding was of high affinity to single classes of receptors (liver: K_d=3.0nM and B_max=530±10 fmol/mg protein, kidney: K_d=0.5±0.9nM and B_max=11±8 fmol/mg protein). Competition of [¹²⁵I]-[d(CH₂)₅, Sar⁷]AVP binding by unlabelled AVP analogues gave the following order of potency in both tissues, consistent with that expected for binding to a V₁ receptor: [d(CH₂)₅, Tyr(Me)²]AVP > AVP > [d(CH₂)₅, D-Ile², Ile⁴] AVP > DDAVP. No degradation of [¹²⁵I]-[d(CH₂)₅, Sar⁷]AVP during incubation or storage was detected by HPLC analysis. We have used [¹²⁵I]-[d(CH₂)₅, Sar⁷]AVP and in vitro autoradiography to demonstrate its use in localizing brain AVP receptors. These studies suggest that [¹²⁵I]-[d(CH₂)₅, Sar⁷]AVP is a suitable selective radioligand for labelling V₁ receptors and will provide a valuable tool for the study of the localization and regulation of AVP V₁ receptors in tissues and in receptor isolation.