title: Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells.
abstract: Clinical and basic science data support an integral role of calcitonin gene-related peptide (CGRP) in migraine pathology. Following trigeminal nerve activation, afferent release of CGRP causes vasodilation while efferent release leads to pain. Although CGRP can also be secreted from cell bodies of trigeminal neurons located within the ganglion, the function of CGRP released in the ganglion is poorly understood. Initially, we showed that SNAP-25, a protein required for CGRP release, was localized in cell bodies of trigeminal ganglia neurons. We also found that satellite glial cells in the ganglia express the CGRP1 receptor protein RAMP1. To determine whether CGRP could directly activate glial cells, primary cultures of rat trigeminal ganglia were utilized to study the effects of CGRP on glial nitric oxide (NO) synthesis and release. Under our culture conditions, >95% of the cells expressed glial fibrillary acidic protein and RAMP1. While weak iNOS staining was observed in glia under basal conditions, CGRP treatment greatly increased glial iNOS expression and NO release. This stimulatory effect was blocked by the CGRP1 receptor antagonist, CGRP(8-37) peptide. Treatment of glial cultures with forskolin or cAMP also increased iNOS expression and stimulated NO release to levels similar to CGRP. To our knowledge, this is the first evidence that activation of CGRP1 receptors regulates glial iNOS and NO release. We propose that following trigeminal nerve activation, CGRP secretion from neuronal cell bodies activates satellite glial cells that release NO and initiate inflammatory events in the ganglia that contribute to peripheral sensitization in migraine.
authors.affiliation: Department of Biology, Missouri State University, Springfield, Missouri 65897, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Carrie V
authors.initials: CV
authors.lastname: Vause
authors.forename: Paul L
authors.initials: PL
authors.lastname: Durham
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C545508:Ramp1 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D005576:Colforsin; D009569:Nitric Oxide; C007293:DAPI; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; D015740:Calcitonin Gene-Related Peptide