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Evidence for endothelin‐B receptor involvement in recurrent airway obstruction in horses
Author(s) -
Venugopal Changaram,
Polikepahad Sumanth,
Holmes Earnestine,
Moore Rustin M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a673-b
Subject(s) - receptor , endothelin receptor , immunohistochemistry , medicine , endocrinology , blot , endothelin 1 , constriction , pathology , biology , gene , biochemistry
Airway hyperreactivity (AH) is the hallmark of human asthma and recurrent airway obstruction (RAO) in horses. Endothelin‐1 (ET‐1) is an inflammatory mediator that causes potent constriction of human and equine airways by binding to ETA and ETB receptors. We investigated the mechanism of ET‐induced AH using pharmacoligical, immunohistochemistry (IHC) and molecular studies. The results showed that bronchial rings of RAO horses contracted significantly greater than those of healthy horses to equal concentrations of ET‐1, suggesting alterations in ET receptors. In addition, ETB receptor affinity was significantly increased in RAO whereas that of ETA remained the same. IHC studies showed that ETA receptor staining increased only in one lobe whereas all other lobes showed a significantly increased staining for ETB receptors. Both ET receptors on the epithelium remained unaltered. Western blotting and IHC techniques showed that expression of ETA and ETB receptors was significantly greater in RAO horses. However, RT‐PCR demonstrated greater mRNA expression only in ETB receptors in RAO horses. Overall, the study indicated invovlement of ETB receptors in equine RAO. Supported by a grants from USDA‐NRI (#2001‐35204‐10809) and EHSP of School of Veterinary Medicine.