RGD Reference Report - Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain. - Rat Genome Database

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Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain.

Authors: Kojima, R  Nozawa, K  Doihara, H  Keto, Y  Kaku, H  Yokoyama, T  Itou, H 
Citation: Kojima R, etal., Eur J Pharmacol. 2014 Jan 15;723:288-93. doi: 10.1016/j.ejphar.2013.11.020. Epub 2013 Nov 28.
RGD ID: 10043376
Pubmed: PMID:24291101   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2013.11.020   (Journal Full-text)

Constipation is a major gastrointestinal motility disorder with clinical need for effective drugs. We previously reported that transient receptor potential ankyrin 1 (TRPA1) is highly expressed in enterochromaffin (EC) cells, which are 5-hydroxytryptamine (5-HT)-releasing cells, and might therefore be a novel target for constipation. Here, we examined the effects of ASP7663, a novel and selective TRPA1 agonist, in constipation models as well as an abdominal pain model. ASP7663 activated human, rat, and mouse TRPA1 and released 5-HT from QGP-1 cells, and oral but not intravenous administration of ASP7663 significantly improved the loperamide-induced delay in colonic transit in mice. While pretreatment with the TRPA1 antagonist HC-030031 and vagotomy both inhibited the ameliorating effect of oral ASP7663 on the colonic transit, both orally and intravenously administered ASP7663 significantly inhibited colorectal distension (CRD)-induced abdominal pain response in rats. Taken together, these results demonstrate that ASP7663 exerts both anti-constipation and anti-abdominal pain actions, the former is likely triggered from the mucosal side of the gut wall via activation of vagus nerves while the latter is assumed to be provoked through systemic blood flow. We conclude that ASP7663 can be an effective anti-constipation drug with abdominal analgesic effect.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TRPA1HumanAbdominal Pain  ISOTrpa1 (Rattus norvegicus) RGD 
Trpa1RatAbdominal Pain  IDA  RGD 
Trpa1MouseAbdominal Pain  ISOTrpa1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Trpa1  (transient receptor potential cation channel, subfamily A, member 1)

Genes (Mus musculus)
Trpa1  (transient receptor potential cation channel, subfamily A, member 1)

Genes (Homo sapiens)
TRPA1  (transient receptor potential cation channel subfamily A member 1)


Additional Information