Searching across hundreds of databases
Calcitonin gene-related peptide (CGRP) is a potent vasodilator and a neuromodulator implicated in the pathophysiology of migraine. It binds to the extracellular domains of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP) 1 that together form the CGRP receptor. Antagonist antibodies against CGRP and its binding site at the receptor are clinically effective in preventing migraine attacks. The blood-brain barrier penetration of these antagonist antibodies is limited, suggesting that a potential peripheral site of action is sufficient to prevent migraine attacks. To further understand the sites of CGRP-mediated signaling in migraine, we used immunohistochemical staining with recently developed antagonist antibodies specifically recognizing a fusion protein of the extracellular domains of RAMP1 and CLR that comprise the CGRP binding pocket at the CGRP receptor in monkey and man. We confirmed binding of the antagonist antibodies to human vascular smooth muscle cells (VSMCs) of dural meningeal arteries and neurons in the trigeminal ganglion, both of which are likely sites of action for therapeutic antibodies in migraine patients. We further used one of these antibodies for detailed mapping on cynomolgus monkey tissue and found antagonist antibody binding sites at multiple levels in the trigeminovascular system: in the dura mater VSMCs, in neurons and satellite glial cells in the trigeminal ganglion, and in neurons in the spinal trigeminal nucleus caudalis. These data reinforce and clarify our understanding of CGRP receptor localization in a pattern consistent with a role for CGRP receptors in trigeminal sensitization and migraine pathology.
Pubmed ID: 27155150 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Mast cell tryptase isolated from human lung
View all literature mentionsThis monoclonal targets Myelin Basic Protein
View all literature mentionsThis monoclonal targets PSD95
View all literature mentionsThis monoclonal targets Synaptophysin
View all literature mentionsThis monoclonal targets Actin, α-Smooth Muscle
View all literature mentionsThis monoclonal targets Neurofilament 200 (Phos. and Non-Phos.) antibody produced in mouse
View all literature mentionsThis monoclonal targets MAP-2 (Microtubule Associated Protein, MAP-2A and -2B)
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets Calcitonin Gene-Related Peptide antibody produced in mouse
View all literature mentionsThis monoclonal targets Myelin Basic Protein
View all literature mentionsThis monoclonal targets PSD95
View all literature mentionsThis monoclonal targets Mast cell tryptase isolated from human lung
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
