Adrenomedullin: receptor and signal transduction.
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 (CGRP(1)) 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). CGRP(1) 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 G(s) and adenylate cyclase activation. We demonstrated that adrenomedullin signalling in cell lines expressing specific adrenomedullin receptors followed this expected pattern.
AstraZeneca, CVGI, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. dave.smith@astrazeneca.com
D M
DM
Smith
H A
HA
Coppock
D J
DJ
Withers
A A
AA
Owji
D L
DL
Hay
T P
TP
Choksi
P
P
Chakravarty
S
S
Legon
D R
DR
Poyner
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D051381:Rats; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D053607:Adrenomedullin