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The pharmacology of adrenomedullin receptors and their relationship to CGRP receptors

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Abstract

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 AM22–52 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 CGRP1 and AM2 receptors and AM could activate both AM1 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.

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Author notes

  1. Debbie L. Hay

    Present address: The Liggins Institute, University of Auckland, 2-6 Park Ave., Grafton, Auckland, New Zealand

Authors and Affiliations

  1. Pharmaceutical Sciences Research Institute, Aston University, B4 7ET, Birmingham, UK

    Debbie L. Hay, Alex C. Conner, Stephen G. Howitt & David R. Poyner

  2. Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, W12 0NN, London, UK

    Debbie L. Hay

  3. AstraZeneca, CVGI, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    David M. Smith

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  1. Debbie L. Hay
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  2. Alex C. Conner
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  3. Stephen G. Howitt
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  5. David R. Poyner
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Correspondence to David R. Poyner.

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Hay, D.L., Conner, A.C., Howitt, S.G. et al. The pharmacology of adrenomedullin receptors and their relationship to CGRP receptors. J Mol Neurosci 22, 105–113 (2004). https://doi.org/10.1385/JMN:22:1-2:105

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  • DOI: https://doi.org/10.1385/JMN:22:1-2:105

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