An abundant and specific binding site for the novel vasodilator adrenomedullin in the rat.

Rat adrenomedullin is a novel 50-amino acid peptide with structural similarities to the calcitonin family of peptides, calcitonin, calcitonin gene-related peptide (CGRP), and islet amyloid polypeptide (IAPP). Using rat [125I]adrenomedullin, specific binding sites were demonstrated in heart, lung, spleen, liver, soleus, diaphragm, gastrocnemius, and spinal cord membranes. The highest binding was present in heart and lung, which was further characterized. These sites exhibited saturation, dissociation, and competition. In rat lung, only rat (IC50 = 5.8 nM) and human (IC50 = 94 nM) adrenomedullin competed with [125I]adrenomedullin. However, in rat heart, rat (IC50 = 0.2 nM) and human (IC50 = 4.2 nM) adrenomedullin, IAPP (IC50 = 240 nM), and CGRP (IC50 = 1050 nM) all competed with [125I] adrenomedullin. Saturation analysis revealed binding capacities and dissociation constants of 2.8 +/- 0.3 pmol/mg protein and 1.3 +/- 0.3 nM, respectively, in lung and 0.47 +/- 0.11 pmol/mg protein and 0.41 +/- 0.14 nM in hea...