Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat

Graeme S. Cottrell, Dirk Roosterman, Juan Carlos Marvizon, B. Song, Elizabeth Wick, Stella Pikios, Helen Wong, Claire Berthelier, Yat Tang, Catia Sternini, Nigel W. Bunnett, Eileen F. Grady

Research output: Contribution to journalArticle

Abstract

Calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and intermedin. Although CGRP is widely expressed in the nervous system, less is known about the localization of CLR and RAMP1. To localize these proteins, we raised antibodies to CLR and RAMP1. Antibodies specifically interacted with CLR and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western blotting and immunofluorescence. Fluorescent CGRP specifically bound to the surface of these cells and CGRP, CLR, and RAMP1 internalized into the same endosomes. CLR was prominently localized in nerve fibers of the myenteric and submucosal plexuses, muscularis externa and lamina propria of the gastrointestinal tract, and in the dorsal horn of the spinal cord of rats. CLR was detected at low levels in the soma of enteric, dorsal root ganglia (DRG), and spinal neurons. RAMPl was also localized to enteric and DRG neurons and the dorsal horn. CLR and RAMP1 were detected in perivascular nerves and arterial smooth muscle. Nerve fibers containing CGRP and intermedin were closely associated with CLR fibers in the gastrointestinal tract and dorsal horn, and CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in the nervous system. However, mRNA encoding RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal horn, suggesting that CLR may associate with other RAMPs in these tissues to form a receptor for additional peptides such as adrenomedullin.

Original languageEnglish (US)
Pages (from-to)239-255
Number of pages17
JournalJournal of Comparative Neurology
Volume490
Issue number3
DOIs
StatePublished - Sep 26 2005

Keywords

  • Calcitonin receptor-like receptor
  • Dorsal horn
  • Myenteric plexus
  • Primary afferent
  • Receptor activity modifying protein
  • Submucosal plexus

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Cottrell, G. S., Roosterman, D., Marvizon, J. C., Song, B., Wick, E., Pikios, S., Wong, H., Berthelier, C., Tang, Y., Sternini, C., Bunnett, N. W., & Grady, E. F. (2005). Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. Journal of Comparative Neurology, 490(3), 239-255. https://doi.org/10.1002/cne.20669