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Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract

Cottrell, G. S., Alemi, F., Kirkland, J. G., Grady, E. F., Corvera, C. U. and Bhargava, A. (2012) Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract. Peptides, 35 (2). pp. 202-211. ISSN 0196-9781

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To link to this item DOI: 10.1016/j.peptides.2012.03.020

Abstract/Summary

Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR.RAMP1 in human disease, little is known about its distribution in the human gastrointestinal (GI) tract, where it participates in inflammation and pain. In this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human stomach, ileum and colon by RT-PCR. We next characterized antibodies that we generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin-immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve bundles in the myenteric plexus and nerve fibers throughout the circular and longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR was found in nerve varicosities of the myenteric plexus and surrounding submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize, but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a functional CGRP receptor were clearly localized in myenteric plexus, where they may form functional cell-surface receptors. IMD, another member of calcitonin peptide family was also found in close proximity to CLR, and like CGRP, did not co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be released locally, where they can mediate their effect on their receptors regulating diverse functions such as inflammation, pain and motility.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
ID Code:30249
Additional Information:Cottrell, Graeme S Alemi, Farzad Kirkland, Jacob G Grady, Eileen F Corvera, Carlos U Bhargava, Aditi DK026743/DK/NIDDK NIH HHS/ DK080787/DK/NIDDK NIH HHS/ FS/08/017/25027/British Heart Foundation/United Kingdom R01 DK080787-02S1/DK/NIDDK NIH HHS/ R01 DK080787-03/DK/NIDDK NIH HHS/ T32 DK007573-21/DK/NIDDK NIH HHS/ T32 DK07573/DK/NIDDK NIH HHS/ Peptides. 2012 Jun;35(2):202-11. Epub 2012 Mar 30.
Publisher:Elsevier

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