Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin

A.C. Conner, J. Simms, D.L. Hay, K. Mahmoud, S.G. Howitt, M. Wheatley, D.R. Poyner

Research output: Contribution to journalArticlepeer-review


RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, allowing the generation of six distinct receptors with preferences for CGRP (CT gene-related peptide) adrenomedullin, amylin and CT. There are three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of receptor pharmacology whereas the transmembrane domain contributes to association of the RAMP with the GPCR. The N-terminus of all members of the RAMP family probably contains two disulphide bonds; a potential third disulphide is found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the ligand and plays a key role in its binding, either directly or indirectly. BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very high selectivity for the human CGRP(1) receptor.
Original languageEnglish
Pages (from-to)843-846
Number of pages4
JournalBiochemical Society Transactions
Issue number5
Publication statusPublished - 2004
EventBioscience 2004 Conference - Glasgow , United Kingdom
Duration: 18 Jul 200422 Jul 2004


  • adrenomedullin
  • calcitonin gene-related peptide
  • CGRP
  • calcitonin receptor-like receptor
  • receptor activity-modifying protein 1
  • RAMP1
  • RAMP2
  • RAMP3


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