Document Detail


Characterization of a calcitonin gene-related peptide release assay in rat isolated distal colon.
MedLine Citation:
PMID:  20162407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The release of calcitonin gene-related peptide (CGRP) plays a key role gastrointestinal tract homeostasis. We aimed to investigate mechanisms that mediate CGRP release from the rat colon in vitro. Colon segments were stimulated and the amount of CGRP released was measured using an enzyme immunoassay. Capsaicin and low pH induced significant increases in CGRP release which was shown to be mediated by TRPV1 activation as demonstrated with the TRPV1 antagonists CTPC and capsazepine. The mast cell degranulator, compound 48/80 significantly increased CGRP release an effect that was blocked in the presence of the mast cell stabilizer, ketotifen and the selective Gi inhibitor benzalkonium chloride. The addition of a mixture of inflammatory mediators containing pro-inflammatory cytokines, 5HT, bradykinin and PGE2 showed no effect at neutral pH but at low pH a significant additive effect was observed. We conclude that CGRP release in the rat distal colon occurs in response to mast cell degranulation, inflammatory mediators, low pH and capsaicin and describe a role for TRPV1 receptors in mediating the response.
Authors:
Rejbinder Kaur; Celestine T O'Shaughnessy; Emma M Jarvie; Wendy J Winchester; Peter G McLean
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2010-02-17
Journal Detail:
Title:  Archives of pharmacal research     Volume:  32     ISSN:  0253-6269     ISO Abbreviation:  Arch. Pharm. Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-05-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000036     Medline TA:  Arch Pharm Res     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  1775-81     Citation Subset:  IM    
Affiliation:
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
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MeSH Terms
Descriptor/Qualifier:
Amiloride / chemistry,  pharmacology
Animals
Anti-Allergic Agents / pharmacology
Benzalkonium Compounds / pharmacology
Calcitonin Gene-Related Peptide / chemistry,  metabolism*
Capsaicin / analogs & derivatives,  chemistry,  pharmacology
Colon / chemistry,  metabolism*
Hydrogen-Ion Concentration
Inflammation Mediators / pharmacology
Ketotifen / pharmacology
Male
Mast Cells / drug effects
Nerve Tissue Proteins / antagonists & inhibitors
Neurons, Afferent / chemistry,  metabolism
Rats
Rats, Sprague-Dawley
Sodium Channels
Solutions
TRPV Cation Channels / antagonists & inhibitors
p-Methoxy-N-methylphenethylamine / pharmacology
Chemical
Reg. No./Substance:
0/ASIC channel; 0/Anti-Allergic Agents; 0/Benzalkonium Compounds; 0/Inflammation Mediators; 0/Nerve Tissue Proteins; 0/Sodium Channels; 0/Solutions; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 0/capsazepine; 2609-46-3/Amiloride; 34580-13-7/Ketotifen; 404-86-4/Capsaicin; 4091-50-3/p-Methoxy-N-methylphenethylamine; 83652-28-2/Calcitonin Gene-Related Peptide

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


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