Journal article
A second trigeminal CGRP receptor: function and expression of the AMY1 receptor
Annals of clinical and translational neurology, Vol.2(6), pp.595-608
06/2015
DOI: 10.1002/acn3.197
PMCID: PMC4479521
PMID: 26125036
Abstract
The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system.
Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human. Receptor pharmacology was quantified using sensitive signaling assays in primary rat TG neurons.
mRNA and histological expression analysis in rat and human samples revealed the presence of two CGRP-responsive receptors (AMY1: calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the CGRP receptor (calcitonin receptor-like receptor/RAMP1). In support of this finding, quantification of agonist and antagonist potencies revealed a dual population of functional CGRP-responsive receptors in primary rat TG neurons.
The unexpected presence of a functional non-canonical CGRP receptor (AMY1) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine.
Details
- Title: Subtitle
- A second trigeminal CGRP receptor: function and expression of the AMY1 receptor
- Creators
- Christopher S Walker - School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New ZealandSajedeh Eftekhari - Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, SwedenRebekah L Bower - School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New ZealandAndrea Wilderman - Departments of Pharmacology and Medicine, University of California at San Diego La Jolla, CaliforniaPaul A Insel - Departments of Pharmacology and Medicine, University of California at San Diego La Jolla, CaliforniaLars Edvinsson - Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, SwedenHenry J Waldvogel - Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand ; Department of Anatomy with Radiology, Faculty of Medical and Health Science, University of Auckland Auckland, 1142, New ZealandMuhammad A Jamaluddin - School of Biological Sciences, University of Auckland Auckland, 1142, New ZealandAndrew F Russo - Department of Molecular Physiology and Biophysics, University of Iowa Iowa City, Iowa ; Department of Neurology, Veterans Affairs Medical Center, University of Iowa Iowa City, IowaDebbie L Hay - School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.2(6), pp.595-608
- DOI
- 10.1002/acn3.197
- PMID
- 26125036
- PMCID
- PMC4479521
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Publisher
- United States
- Grant note
- R01 NS075599 / NINDS NIH HHS
- Language
- English
- Date published
- 06/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020638702771
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