The pharmacology of adrenomedullin receptors and their relationship to CGRP receptors

Debbie L. Hay, Alex C. Conner, Stephen G. Howitt, David M. Smith, David Poyner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Adrenomedullin (AM) has two specific receptors formed by the calcitonin-receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3. These are known as AM1 and AM2 receptors, respectively. In addition, AM has appreciable affinity for the CGRP1 receptor, composed of CL and RAMP1. The AM1 receptor has a high degree of selectivity for AM over CGRP and other peptides, and AM 22-52 is an effective antagonist at this receptor. By contrast, the AM2 receptor shows less specificity for AM, having appreciable affinity for βCGRP. Here, CGRP8-37 is either equipotent or more effective as an antagonist than AM22-52, depending on the species from which the receptor components are derived. Thus, under the appropriate circumstances it seems that βCGRP might be able to activate both CGRP 1 and AM2 receptors and AM could activate both AM 1 and AM2 receptors as well as CGRP1 receptors. Current peptide antagonists are not sufficiently selective to discriminate between these three receptors. The CGRP-selectivity of RAMP1 and RAMP3 may be conferred by a putative disulfide bond from the N-terminus to the middle of the extracellular domain of these molecules. This is not present in RAMP2. Copyright © 2004 Humana Press Inc. All rights of any nature whatsoever reserved.

Original languageEnglish
Pages (from-to)105-113
Number of pages9
JournalJournal of Molecular Neuroscience
Issue number1-2
Publication statusPublished - 1 Feb 2004


  • adrenomedullin
  • calcitonin receptor-like receptor
  • CGRP
  • CL
  • RAMP2
  • RAMP3


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