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

We have investigated the binding characteristics of rat [I-125] adrenomedul lin (AM) and human [I-125] calcitonin gene-related peptide (CGRP) to membra nes prepared from a number of porcine tissues including atrium, ventricle, lung, spleen, liver, renal cortex and medulla. These membranes displayed sp ecific, high affinity binding for [I-125] rat AM and [I-125] human CGRP. Po rcine lung displayed the highest density of binding sites for radiolabeled AM and CGRP followed by porcine renal cortex. Competition experiments perfo rmed with [I-125] rat AM indicated that the rank order of potencies of vari ous peptides for inhibiting [I-125] rat AM binding to various tissues were rat AM 2 human AM 2 human AM(22-52)> h alpha CGRP greater than or equal to 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). Whe n the same experiments were performed using [I-125] h alpha CGRP as the rad ioligand, 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 [I-125] h alpha CGRP bin ding. These data suggest the existence of distinct CGRP and AM specific bin ding sites in contrast to previous reports that showed that both peptides i nteract differently in rat tissues.