Receptor activity modifying proteins regulate the activity of a calcitonin gene‐related peptide receptor in rabbit aortic endothelial cells

FEBS Letters

Born, Walter²  Fischer, Jan A.²  Bühlmann, Nicole²  Muff, Roman²  Foord, Steven M.¹  Leuthäuser, Kerstin² 

[1] Receptor Systems Unit, Glaxo Wellcome Medicine Research Center, Gunnels Wood Road, Stevenage SG1 2NY, UK;Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstrasse 340, 8008 Zurich, Switzerland

关键词: Neuropeptide;    Signal transduction;    Receptor expression;    Vascular cell;    ADM;    adrenomedullin;    CGRP;    calcitonin gene-related peptide;    CRLR;    calcitonin receptor-like receptor;    RAEC;    rabbit aortic endothelial cells;    RAMP;    receptor activity modifying protein;   

DOI  :  10.1016/S0014-5793(98)01587-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 EC₅₀ 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 (EC₅₀ 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.

【 授权许可】

Unknown