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Receptor activity modifying proteins regulate the activity of a calcitonin gene‐related peptide receptor in rabbit aortic endothelial cells
Author(s) -
Muff Roman,
Leuthäuser Kerstin,
Bühlmann Nicole,
Foord Steven M.,
Fischer Jan A.,
Born Walter
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01587-7
Subject(s) - calcitonin gene related peptide , chemistry , endocrinology , adrenomedullin , calcitonin receptor , receptor , medicine , microbiology and biotechnology , receptor antagonist , antagonist , biology , biochemistry , neuropeptide
In Xenopus oocytes with an endogenous calcitonin gene‐related peptide (CGRP) receptor, a receptor activity modifying protein (RAMP1) enhancing CGRP stimulated chloride currents of the cystic fibrosis transmembrane regulator was recently cloned [McLatchie, L.M. et al. (1998) Nature 393, 333–339]. Here, transient expression of RAMP1 in rabbit aortic endothelial cells (RAEC) brought about stimulation of cAMP accumulation by human (h) αCGRP with an EC 50 of 0.41 nM. This was antagonized by a CGRP receptor antagonist αCGRP(8–37). Co‐expression of RAMP3 together with RAMP1 reduced the maximal cAMP response to hαCGRP by 47% ( P <0.05). The cells also express RAMP2 encoding mRNA and an adrenomedullin (ADM) receptor coupled to stimulation of cAMP formation by hADM (EC 50 0.18 nM). The latter was antagonized by an ADM receptor antagonist hADM(22–52). In conclusion, expression of a CGRP receptor in RAEC requires RAMP1. The same receptor presumably recognizes ADM making use of endogenous RAMP2. The results reveal competition between the different RAMPs in the regulation of CGRP/ADM receptor activity.