Endocrinology, Vol 137, 3260-3264, Copyright © 1996 by Endocrine Society

ARTICLES

Adrenomedullin inhibits feeding in the rat by a mechanism involving calcitonin gene-related peptide receptors

GM Taylor, K Meeran, D O'Shea, DM Smith, MA Ghatei and SR Bloom
Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

The central effect of adrenomedullin on feeding was investigated in fasted rats. After intracerebroventricular administration, adrenomedullin decreased 2-h food intake in a dose-dependent manner. A dose of 1.7 nmol adrenomedullin decreased 2-h food intake by 57%. Adrenomedullin shares sequence homology with calcitonin gene-related peptide (CGRP), a central anorectic agent, and binding sites for both are present in the hypothalamus. Adrenomedullin competed for [125I]adrenomedullin- and [125I]CGRP-binding sites in hypothalamic membranes. The Kd for the [125I]adrenomedullin-binding site was 0.54 +/- 0.07 nM, with a binding capacity of 214 +/- 27 fmol/mg membrane protein (n = 3). CGRP and the CGRP receptor antagonist CGRP-(8-37) at concentrations up to 1 microM did not compete at these sites. The Kd for the CGRP-binding site was 0.10 +/- 0.02 nM, with a binding capacity of 250 +/- 31 fmol/mg, and the Ki values for adrenomedullin and CGRP-(8- 37) were 4.6 +/- 2.1 and 4.0 +/- 1.6 nM, respectively (n = 3). Thus, adrenomedullin showed high affinity binding at both adrenomedullin- and CGRP-binding sites. To establish whether adrenomedullin reduces feeding via CGRP receptors, we coadministered adrenomedullin (1.7 nmol) and CGRP-(8-37) (30 nmol). The reduction in 2-h food intake induced by adrenomedullin was 50% inhibited by CGRP-(8-37). These results show that adrenomedullin decreases food intake in the rat, and this effect is mediated at least in part via CGRP receptors.

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