A second trigeminal CGRP receptor: function and expression of the AMY1 receptor
Christopher S Walker1, Sajedeh Eftekhari2, Rebekah L Bower1
1School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand.
Annals of Clinical and Translational Neurology
|July 1, 2015
Summary
Researchers found two calcitonin gene-related peptide (CGRP) receptors in the trigeminal system, including a non-canonical receptor (AMY1). This discovery impacts migraine treatment strategies targeting the CGRP pathway.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The trigeminovascular system is implicated in migraine pathophysiology.
- Calcitonin gene-related peptide (CGRP) is a key neuropeptide in migraine and a target for drug development.
Purpose of the Study:
- To investigate the expression and function of CGRP receptor candidates in the sensory trigeminal system.
- To explore potential therapeutic targets for migraine treatment.
Main Methods:
- Utilized Taqman G protein-coupled receptor arrays and immunohistochemistry to analyze receptor expression in rat and human trigeminal ganglia and spinal trigeminal complex.
- Employed signaling assays in primary rat trigeminal ganglia neurons to quantify receptor pharmacology.
Main Results:
- Identified mRNA and histological evidence for two CGRP-responsive receptors: AMY1 (calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the canonical CGRP receptor (calcitonin receptor-like receptor/RAMP1) in both rat and human samples.
- Demonstrated a dual population of functional CGRP-responsive receptors in primary rat trigeminal ganglia neurons through agonist and antagonist potency quantification.
Conclusions:
- The study unexpectedly found a functional non-canonical CGRP receptor (AMY1) in neural pathways crucial for craniofacial pain.
- This finding has significant implications for developing novel migraine therapies by targeting the CGRP signaling axis.
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