Article: article from journal or magazin.
Characterization of a novel, linear radioiodinated vasopressin antagonist: an excellent radioligand for vasopressin V1a receptors
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Aug
We report on the pharmacological properties of a potent and selective linear vasopressin (AVP) V1a receptor antagonist HO-Phenylacetyl1-D-Tyr(Me)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-NH2 (HO-LVA). Iodinated on the phenolic substituent at position 1, [125I]-HO-LVA displayed the highest affinity for rat liver V1a receptors (8 pM) ever reported. Furthermore, affinities of HO-LVA and I-HO-LVA for V1b, V2 and oxytocin (OT) receptors was 400- to 1,000-fold lower than for V1a receptors, rendering it a highly selective ligand. Both HO-LVA and its iodinated derivative are V1 antagonists, they potently inhibited AVP-induced inositol-phosphate accumulation in WRK1 cells, and also, although with a much lower potency, the AVP-induced ACTH release from freshly prepared pituitary cells. Using autoradiography [125I]-HO-LVA appeared to be the first radioligand to successfully identify and localize the presence of V1a receptors in rat liver and blood vessel walls. Moreover, several new brain regions expressing V1a receptors could be identified, in addition to those brain regions that were previously identified with other radiolabelled AVP analogues.
Adrenocorticotropic Hormone/secretion Amino Acid Sequence Animals Arginine Vasopressin/pharmacology Autoradiography Cell Membrane/metabolism Female Inositol Phosphates/metabolism *Iodine Radioisotopes Liver/metabolism Mammary Neoplasms, Experimental Molecular Sequence Data Oligopeptides/*metabolism/pharmacology Pituitary Gland/drug effects/secretion Rats Rats, Wistar Receptors, Oxytocin/metabolism Receptors, Vasopressin/analysis/*metabolism Tissue Distribution Tumor Cells, Cultured Vasopressins/*antagonists & inhibitors
Web of science
Last modification date