[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-(beta-mercapto-beta, beta-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: Kd = 3.0 nM and Bmax = 530 +/- 10 fmol/mg protein, kidney: Kd = 0.5 +/- 0.9 nM and Bmax = 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 greater than AVP greater than [d(CH2)5, D-Ile2, Ile4] AVP greater than 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.