Open AccessA second trigeminal CGRP receptor: function and expression of the AMY 1 receptor
Author(s) -
Walker Christopher S.,
Eftekhari Sajedeh,
Bower Rebekah L.,
Wilderman Andrea,
Insel Paul A.,
Edvinsson Lars,
Waldvogel Henry J.,
Jamaluddin Muhammad A.,
Russo Andrew F.,
Hay Debbie L.
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.197
Subject(s) - calcitonin gene related peptide , receptor , trigeminal ganglion , calcitonin receptor , medicine , endocrinology , agonist , receptor expression , population , pharmacology , neuropeptide , neuroscience , biology , sensory system , environmental health
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 ( AMY 1 : calcitonin receptor/receptor activity‐modifying protein 1 [ RAMP 1]) and the CGRP receptor (calcitonin receptor‐like receptor/ RAMP 1). 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 ( AMY 1 ) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine.