Comparative affinities of adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) for [125I] AM and [125I] CGRP specific binding sites in porcine tissues.
We have investigated the binding characteristics of rat [125I] adrenomedullin (AM) and human [125I] 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 [125I] rat AM and [125I] human CGRP. Porcine lung displayed the highest density of binding sites for radiolabeled AM and CGRP followed by porcine renal cortex. Competition experiments performed with [125I] rat AM indicated that the rank order of potencies of various peptides for inhibiting [125I] rat AM binding to various tissues were rat AM > or = human AM > or = human AM(22-52) > h alpha CGRP > or = 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 [125I] 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 [125I] h alpha CGRP binding. These data suggest the existence of distinct CGRP and AM specific binding sites in contrast to previous reports that showed that both peptides interact differently in rat tissues.
Dang
K
K
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Disa
J
J
Gout
B
B
Aiyar
N
N
D053607:Adrenomedullin; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D009928:Organ Specificity; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D013552:Swine
D007457:Iodine Radioisotopes; D010455:Peptides; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide