Adrenomedullin: receptor and signal transduction. (August 2002)

• Record Type: Journal Article
• Authors: Smith, D. M.; Coppock, H. A.; Withers, D. J.; Owji, A. A.; Hay, D. L.; Choksi, T. P.; Chakravarty, P.; Legon, S.; Poyne, D. R.
• Is Part Of: Biochemical Society transactions. Volume 30:Number 4(2002)
• Page Start: 432
• Page End: 437
• Publication Date: 2002-08
• Subjects: calcitonin -- calcitonin-receptor-like receptor (CRLR) -- receptor-activity-modifying protein (RAMP) -- type II G-protein-coupled receptor (GPCR); CGRP, calcitonin-gene-related peptide -- CRLR, calcitonin-receptor-like receptor -- GPCR, G-protein-coupled receptor -- MAPK, mitogen-activated protein kinase -- PDGF, platelet-derived growth factor -- RAMP, receptor-activity-modifying protein; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0300432
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Adrenomedullin is a vascular tissue peptide and a member of the calcitonin family of peptides, which includes calcitonin, calcitonin-gene-related peptide (CGRP) and amylin. Its many biological actions are mediated via CGRP type 1 (CGRP1 ) receptors and by specific adrenomedullin receptors. Although the pharmacology of these receptors is distinct, they are both represented in molecular terms by the type II family G-protein-coupled receptor, calcitonin-receptor-like receptor (CRLR). The specificity here is defined by co-expression of receptor-activity-modifying proteins (RAMPs). CGRP1 receptors are represented by CRLR and RAMP1, and specific adrenomedullin receptors by CRLR and RAMP2 or 3. Here we discuss how CRLR/RAMP2 relates to adrenomedullin binding, pharmacology and pathophysiology, and how chemical cross-linking of receptor-ligand complexes in tissue relates to that in CRLR/RAMP2-expressing cells. CRLR, like other type II family G-protein-coupled receptors, signals via Gs and adenylate cyclase activation. We demonstrated that adrenomedullin signalling in cell lines expressing specific adrenomedullin receptors followed this expected pattern.