Specific adrenomedullin binding sites in the human brain

Binding sites for adrenomedullin in human brain were investigated and characterized by radioligand binding. Specific binding sires for adrenomedullin were present in every region of human brain (cerebral cortex, cerebellum, thalamus, hypothalamus, Dens and medulla oblongata) obtained at autopsy. Despite the homology with calcitonin gene-related peptide (CGRP), CGRP was a poor inhibitor of [(125)]adrenomedullin binding (IC50 > 1 mu M) compared with adrenomedullin(1-52) (IC50 = 1.2 +/- 0.5 nM, mean +/- SEM, n = 3). Three adrenomedullin fragments, adrenomedullin(1-12), adrenomedullin(22-52), and adrenomedullin(13-52), were also poor inhibitors of the binding (IC50 = 0.3 mu M), suggesting that the whole molecule of adrenomedullin(1-52) is required for binding to the receptor. Scatchard plots of [I-125]adrenomedullin binding in human brain (cerebral cortex) gave a dissociation constant of 0.17 +/- 0.03 nM and maximal binding of 99.3 +/- 1.9 fmol/mg protein (n = 5). These findings suggest that specific adrenomedullin binding sites that differ from the CGRP receptors exist in human brain. This indicates a possible novel neurotransmitter/neuromodulator role for adrenomedullin in human brain. (C) 1997 Elsevier Science Inc.