Comparative affinities of adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) for [~(125)I] AM and [~(125)I] CGRP specific binding sites in porcine tissues

摘要

We have investigated the binding characteristics of rat [~(125)I] adrenomedullin (AM) and human [~(125)I] calcitonin gene-related peptide (CGRP) to membranes prepared from a number of porcine tissues including atrium, ventricle, lung, spleen, liver, renal cortex and medulla. These membranes displayed specific, high affinity binding for [~(125)I] rat AM and [~(125)I] human CGRP. Porcine lung displayed the highest density of binding sites for radiolabeled AM and CTRP followed by porcine renal cortex. Competition experiments performed with [~(125)I] rat AM indicated that the rank order of potencies of various petides for inhibiting [~(125)I] rat AM binding to various tissues were rat AM >= human AM >= human AM(22-52) > h#alpha#CGRP >= h#alpha#CGRP(8-37) sCT except spleen, atrium, renal cortex and renal medulla where rAM and hAM were 20-300 fold more potent than hAM(22-52). When the same experiments were performed using [~(125)I]h#alpha#CGRP as the radioligand, the rank order potencies for various peptides were rAM = hAM > h#alpha#CGRP > h#alpha#CGRP(8-37) in most of the tissues except in spleen and liver. Where h#alpha#CGRP was the most potent ligand. In lung, h#alpha#CGRP was almost as potent as rAM and hAM in displacing [~(125)I] h#alpha#CGRP binding. These data suggest the existence of distance CGRP and AM specific binding sites in contrast to previous reports that showed that both peptides interact differently in rat tissues.