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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

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. and 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). pp. 239-255. ISSN 1096-9861

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To link to this item DOI: 10.1002/cne.20669


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. RAMP1 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.

Item Type:Article
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
No Reading authors. Back catalogue items
ID Code:30280
Uncontrolled Keywords:Animals Binding Sites Blotting, Northern/methods Blotting, Western/methods Calcitonin Gene-Related Peptide/metabolism Cell Line Enteric Nervous System/*cytology Ganglia, Spinal/*metabolism Humans Immunohistochemistry/methods Intracellular Signaling Peptides and Proteins/genetics/*metabolism Lectins/metabolism Membrane Proteins/genetics/*metabolism Neurons/*metabolism Protein Binding Pyrrolizidine Alkaloids/metabolism RNA, Messenger/biosynthesis Rats Receptor Activity-Modifying Protein 1 Receptor Activity-Modifying Protein 2 Receptor Activity-Modifying Protein 3 Receptor Activity-Modifying Proteins Receptors, Calcitonin/genetics/*metabolism Reverse Transcriptase Polymerase Chain Reaction/methods Spinal Cord/*metabolism Substance P Transfection
Additional Information:Cottrell, Graeme S Roosterman, Dirk Marvizon, Juan-Carlos Song, B Wick, Elizabeth Pikios, Stella Wong, Helen Berthelier, Claire Tang, Yat Sternini, Catia Bunnett, Nigel W Grady, Eileen F DA 12609/DA/NIDA NIH HHS/ DK 39957/DK/NIDDK NIH HHS/ DK 41301/DK/NIDDK NIH HHS/ DK 52388/DK/NIDDK NIH HHS/ DK 54155/DK/NIDDK NIH HHS/ DK 57037/DK/NIDDK NIH HHS/ DK 57840/DK/NIDDK NIH HHS/ P50 DA005010/DA/NIDA NIH HHS/ J Comp Neurol. 2005 Sep 26;490(3):239-55.

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