Document Detail


Repression of stimulated calcitonin gene-related peptide secretion by topiramate.
MedLine Citation:
PMID:  16942474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paul L Durham; Christine Niemann; Roger Cady
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Headache     Volume:  46     ISSN:  0017-8748     ISO Abbreviation:  Headache     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-31     Completed Date:  2007-02-13     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  2985091R     Medline TA:  Headache     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1291-5     Citation Subset:  IM    
Affiliation:
Department of Biology, Missouri State University, Springfield, MO, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcitonin Gene-Related Peptide / drug effects*,  secretion
Cells, Cultured
Dose-Response Relationship, Drug
Fructose / analogs & derivatives*,  pharmacology
Neurons / cytology,  drug effects*,  metabolism
Neuroprotective Agents / pharmacology
Nitric Oxide Donors / pharmacology
Penicillamine / analogs & derivatives,  pharmacology
Potassium Chloride / pharmacology
Rats
Rats, Sprague-Dawley
Trigeminal Ganglion / cytology,  drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Nitric Oxide Donors; 0/S-nitro-N-acetylpenicillamine; 0H73WJJ391/topiramate; 30237-26-4/Fructose; 52-67-5/Penicillamine; 7447-40-7/Potassium Chloride; 83652-28-2/Calcitonin Gene-Related Peptide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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