RGD Reference Report - The role of ET(A) and ET(B) receptor antagonists in acute and allergic inflammation in mice. - Rat Genome Database

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The role of ET(A) and ET(B) receptor antagonists in acute and allergic inflammation in mice.

Authors: Kassuya, CA  Rogerio, AP  Calixto, JB 
Citation: Kassuya CA, etal., Peptides. 2008 Aug;29(8):1329-37. Epub 2008 Mar 16.
RGD ID: 4892288
Pubmed: PMID:18632188   (View Abstract at PubMed)
DOI: DOI:10.1016/j.peptides.2008.03.008   (Journal Full-text)

In this study, we investigated the effects of the selective ET(A) (BQ-123) and ET(B) (BQ-788) receptor antagonists for endothelin-1 (ET-1) against several flogistic agent-induced paw edema formation and ovalbumin-induced allergic lung inflammation in mice. The intraplantar injection of BQ-123, but not BQ-788, significantly inhibited carrageenan-, PAF-, ET-1- and bradykinin-induced paw edema formation. The obtained inhibitions (1h after the inflammatory stimulus) were 79+/-5%, 55+/-4%, 55+/-6% and 74+/-4%, respectively. In carrageenan-induced paw edema, the mean ID(50) value for BQ-123 was 0.77 (0.27-2.23)nmol/paw. The neutrophil influx induced by carrageenan or PAF was reduced by BQ-123, with inhibitions of 55+/-2% and 72+/-4%, respectively. BQ-123 also inhibited the indirect macrophage influx induced by carrageenan (55+/-6%). However, BQ-788 failed to block the cell influx caused by either of these flogistic agents. When assessed in the bronchoalveolar lavage fluid in a murine model of asthma, both BQ-123 and BQ-788 significantly inhibited ovalbumin-induced eosinophil recruitment (78+/-6% and 71+/-8%), respectively. Neither neutrophil nor mononuclear cell counts were significantly affected by these drugs. Our findings indicate that ET(A), but not ET(B), selective ET-1 antagonists are capable of preventing the acute inflammatory responses induced by carrageenan, PAF, BK and ET-1. However, both ET(A) and ET(B) receptor antagonists were found to be effective in inhibiting the allergic response in a murine model of asthma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOEdnra (Mus musculus)4892288; 4892288 RGD 
asthma  ISOEdnrb (Mus musculus)4892288; 4892288 RGD 
asthma  IMP 4892288; 4892288 RGD 
Inflammation  ISOEdnra (Mus musculus)4892288; 4892288 RGD 
Inflammation  IMP 4892288 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ednra  (endothelin receptor type A)
Ednrb  (endothelin receptor type B)

Genes (Mus musculus)
Ednra  (endothelin receptor type A)
Ednrb  (endothelin receptor type B)

Genes (Homo sapiens)
EDNRA  (endothelin receptor type A)
EDNRB  (endothelin receptor type B)


Additional Information