[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.
Kelly
J M
JM
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Abrahams
J M
JM
Phillips
P A
PA
Mendelsohn
F A
FA
Grzonka
Z
Z
Johnston
C I
CI
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001345:Autoradiography; D007457:Iodine Radioisotopes; D007668:Kidney / Q000032:analysis; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis*; D017483:Receptors, Vasopressin
D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; C058531:argipressin, (1-beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-Sar(7)-; D001127:Arginine Vasopressin