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Walker CS, Eftekhari S, Bower RL, et al. A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Transl Neurol. 2015;2(6):595-608doi: 10.1002/acn3.197.
Walker, C. S., Eftekhari, S., Bower, R. L., Wilderman, A., Insel, P. A., Edvinsson, L., Waldvogel, H. J., Jamaluddin, M. A., Russo, A. F., & Hay, D. L. (2015). A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Annals of clinical and translational neurology, 2(6), 595-608. https://doi.org/10.1002/acn3.197
Walker, Christopher S, et al. "A second trigeminal CGRP receptor: function and expression of the AMY1 receptor." Annals of clinical and translational neurology vol. 2,6 (2015): 595-608. doi: https://doi.org/10.1002/acn3.197
Walker CS, Eftekhari S, Bower RL, Wilderman A, Insel PA, Edvinsson L, Waldvogel HJ, Jamaluddin MA, Russo AF, Hay DL. A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Transl Neurol. 2015 Jun;2(6):595-608. doi: 10.1002/acn3.197. Epub 2015 Apr 01. PMID: 26125036; PMCID: PMC4479521.
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Ann Clin Transl Neurol. 2015 Jun;2(6):595-608. doi: 10.1002/acn3.197. Epub 2015 Apr 01.

A second trigeminal CGRP receptor: function and expression of the AMY1 receptor.

Annals of clinical and translational neurology

Christopher S Walker, Sajedeh Eftekhari, Rebekah L Bower, Andrea Wilderman, Paul A Insel, Lars Edvinsson, Henry J Waldvogel, Muhammad A Jamaluddin, Andrew F Russo, Debbie L Hay

Affiliations

  1. School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand.
  2. Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, Sweden.
  3. Departments of Pharmacology and Medicine, University of California at San Diego La Jolla, California.
  4. 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 Zealand.
  5. School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand.
  6. Department of Molecular Physiology and Biophysics, University of Iowa Iowa City, Iowa ; Department of Neurology, Veterans Affairs Medical Center, University of Iowa Iowa City, Iowa.

PMID: 26125036 PMCID: PMC4479521 DOI: 10.1002/acn3.197

Abstract

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

INTERPRETATION: 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.

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