title: A second trigeminal CGRP receptor: function and expression of the AMY1 receptor.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Walker
authors.affiliation: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, Sweden.
authors.forename: Sajedeh
authors.initials: S
authors.lastname: Eftekhari
authors.affiliation: School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand.
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Bower
authors.affiliation: Departments of Pharmacology and Medicine, University of California at San Diego La Jolla, California.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilderman
authors.affiliation: Departments of Pharmacology and Medicine, University of California at San Diego La Jolla, California.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
authors.affiliation: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
authors.affiliation: 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.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Waldvogel
authors.affiliation: School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Jamaluddin
authors.affiliation: 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.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Russo
authors.affiliation: School of Biological Sciences, University of Auckland Auckland, 1142, New Zealand ; Centre for Brain Research, University of Auckland Auckland, 1142, New Zealand.
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Hay