Repression of stimulated calcitonin gene-related peptide secretion by topiramate.
OBJECTIVE
The goal of the proposed research was to determine the effect of topiramate on basal and stimulated release of calcitonin gene-related peptide (CGRP) from trigeminal ganglia neurons.


BACKGROUND
CGRP is implicated in migraine headaches. Clinical evidence supports topiramate as an effective migraine prophylactic. In this study, the connection between topiramate and CGRP expression was investigated.


METHODS
Primary cultures of rat trigeminal ganglia were utilized to determine the effects of topiramate on CGRP release stimulated by a depolarizing stimulus (KCl), nitric oxide, and/or protons. The amount of CGRP secreted into the culture media was determined using a CGRP-specific radioimmunoassay.


RESULTS
Treatment of trigeminal cultures with KCl, nitric oxide donor S-nitroso-N-acetylpenicillamine, or protons (pH 5.5 media) caused a marked increase (3 to 5 fold) in the amount of CGRP release. Topiramate treatment repressed KCl-stimulated CGRP release in a time- and concentration-dependent manner. However, topiramate did not alter the amount of unstimulated or basal CGRP released from trigeminal neurons. In addition, topiramate inhibited nitric oxide and proton mediated CGRP secretion.


CONCLUSIONS
Findings from these studies demonstrate that topiramate can directly repress the stimulated release of CGRP from sensory trigeminal neurons. We propose that topiramate's ability to prevent migraine attacks may involve inhibition of CGRP secretion from trigeminal neurons.
Durham
Paul L
PL
Department of Biology, Missouri State University, Springfield, MO, USA.
Niemann
Christine
C
Cady
Roger
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077236:Topiramate; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D000077236:Topiramate; D005632:Fructose; D011189:Potassium Chloride; D010396:Penicillamine; D015740:Calcitonin Gene-Related Peptide