Specific adrenomedullin binding sites in the human brain

Masahiko Sone, Kazuhiro Takahashi, Fumitoshi Satoh, Osamu Murakami, Kazuhito Totsune, Makoto Ohneda, Hironobu Sasano, Hisao Ito, Toraichi Mouri

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Binding sites for adrenomedullin in human brain were investigated and characterized by radioligand binding. Specific binding sites for adrenomedullin were present in every region of human brain (cerebral cortex, cerebellum, thalamus, hypothalamus, pons and medulla oblongata) obtained at autopsy. Despite the homology with calcitonin gene-related peptide (CGRP). CGRP was a poor inhibitor of [125I]adrenomedullin binding (IC50 >1 μM) 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 μM), suggesting that the whole molecule of adrenomedullin(1- 52) is required for binding to the receptor. Scatchard plots of [125I]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.

Original languageEnglish
Pages (from-to)1125-1129
Number of pages5
JournalPeptides
Volume18
Issue number8
DOIs
Publication statusPublished - 1997 Dec 1

Keywords

  • Adrenomedullin
  • Calcitonin gene related peptide
  • Human brain
  • Receptor

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Sone, M., Takahashi, K., Satoh, F., Murakami, O., Totsune, K., Ohneda, M., Sasano, H., Ito, H., & Mouri, T. (1997). Specific adrenomedullin binding sites in the human brain. Peptides, 18(8), 1125-1129. https://doi.org/10.1016/S0196-9781(97)00143-5