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Rigshospitalet - a part of Copenhagen University Hospital
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A second trigeminal CGRP receptor: function and expression of the AMY1 receptor

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  2. Expression of the CGRP Family of Neuropeptides and their Receptors in the Trigeminal Ganglion

    Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
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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.

Original languageEnglish
JournalAnnals of Clinical and Translational Neurology
Volume2
Issue number6
Pages (from-to)595-608
Number of pages14
DOIs
Publication statusPublished - Jun 2015
Externally publishedYes

ID: 45640206