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.
Smith
D M
DM
AstraZeneca, CVGI, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. dave.smith@astrazeneca.com
Coppock
H A
HA
Withers
D J
DJ
Owji
A A
AA
Hay
D L
DL
Choksi
T P
TP
Chakravarty
P
P
Legon
S
S
Poyner
D R
DR
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