Open AccessActivation of transient receptor potential ankyrin 1 induces CGRP release from spinal cord synaptosomes
Author(s) -
Quallo Talisia,
Gentry Clive,
Bevan Stuart,
Broad Lisa M.,
Mogg Adrian J.
Publication year - 2015
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.191
Subject(s) - transient receptor potential channel , calcitonin gene related peptide , spinal cord , chemistry , dorsal root ganglion , voltage dependent calcium channel , nociception , agonist , depolarization , calcium channel , ankyrin , neuroscience , biophysics , endocrinology , medicine , calcium , receptor , neuropeptide , biology , biochemistry , organic chemistry , gene
Transient receptor potential ankyrin 1 ( TRPA 1) is a sensor of nociceptive stimuli, expressed predominantly in a subpopulation of peptidergic sensory neurons which co‐express the noxious heat‐sensor transient receptor potential vanilloid 1. In this study, we describe a spinal cord synaptosome‐calcitonin gene‐related peptide ( CGRP ) release assay for examining activation of TRPA 1 natively expressed on the central terminals of dorsal root ganglion neurons. We have shown for the first time that activation of TRPA 1 channels expressed on spinal cord synaptosomes by a selection of agonists evokes a concentration‐dependent release of CGRP which is inhibited by TRPA 1 antagonists. In addition, our results demonstrate that depolarization of spinal cord synaptosomes by a high concentration of KCl induces CGRP release via a T‐type calcium channel‐dependent mechanism whilst TRPA 1‐induced CGRP release functions independently of voltage‐gated calcium channel activation. Finally, we have shown that pre‐treatment of synaptosomes with the opioid agonist, morphine, results in a reduction of depolarization‐induced CGRP release. This study has demonstrated the use of a dorsal spinal cord homogenate assay for investigation of natively expressed TRPA 1 channels and for modulation of depolarizing stimuli at the level of the dorsal spinal cord.