title: Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.
abstract: Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.
authors.affiliation: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wild
authors.affiliation: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Messlinger
authors.affiliation: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany. Electronic address: fischer@physiologie1.uni-erlangen.de.
authors.forename: Michael J M
authors.initials: MJ
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism*; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000378:metabolism
chemical_list: D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D013440:Sulfides; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C039900:nitroxyl; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: Brainstem; CGRP; Headache; Migraine; Neuropeptide; Nociception