title: Release of CGRP from mouse brainstem slices indicates central inhibitory effect of triptans and kynurenate.
abstract: BACKGROUND
  CGRP is contained in a substantial proportion of unmyelinated trigeminal neurons innervating intracranial tissues. Previously, we have described a hemisected rodent scull preparation and later the intact trigeminal ganglion to measure stimulated CGRP release from trigeminal afferents.
  
  
  METHODS
  Here, we establish a preparation for examining CGRP release from central trigeminal terminals using single fresh slices of the mouse medullary brainstem.
  
  
  RESULTS
  Basal and stimulated amount of CGRP substantially exceeded the detection level. Experiments were designed as matched pairs of at least six brainstem slices per animal. Stimulation with high potassium induced calcium-dependent and reversible CGRP release. Capsaicin stimulation of TRPV1 provoked concentration-dependent CGRP release. The anti-migraine drug naratriptan did not inhibit capsaicin-induced CGRP release from peripheral terminals but inhibited the release from brainstem slices. The glutamate antagonist kynurenate showed a similar pattern of site-specific inhibition of CGRP release.
  
  
  CONCLUSIONS
  As observed earlier for other drugs used in the treatment of migraine this indicates that the central terminals in the spinal trigeminal nucleus may be the main site of action. The preparation allows evaluating the trigeminal brainstem as a pharmacological site of action.
authors: Charlotte
authors: C
authors: Kageneck
authors: Barbara E
authors: BE
authors: Nixdorf-Bergweiler
authors: Karl
authors: K
authors: Messlinger
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Universitaetsstrasse, 91054 Erlangen, Germany. fischer@physiologie1.uni-erlangen.de.
authors: Michael Jm
authors: MJ
authors: Fischer
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D010880:Piperidines; D014363:Tryptamines; D007736:Kynurenic Acid; D015740:Calcitonin Gene-Related Peptide; C106783:naratriptan; D002211:Capsaicin