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Titolo:
The role of endothelin in mediating virus-induced changes in endothelin(B)receptor density in mouse airways
Autore:
Henry, PJ; Carr, MJ; Goldie, RG; Jeng, AY;
Indirizzi:
Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia Univ Western Australia Nedlands WA Australia 6907 nds, WA 6907, Australia Novartis Inst Biomed Res, Summit, NJ USA Novartis Inst Biomed Res Summit NJ USA s Inst Biomed Res, Summit, NJ USA
Titolo Testata:
EUROPEAN RESPIRATORY JOURNAL
fascicolo: 1, volume: 14, anno: 1999,
pagine: 92 - 97
SICI:
0903-1936(199907)14:1<92:TROEIM>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRACT VIRAL-INFECTION; NEUTRAL ENDOPEPTIDASE NEP; TRACHEAL SMOOTH-MUSCLE; EPITHELIAL-CELLS; EXPRESSION; MICE; ET(B); IMMUNOREACTIVITY; INFLAMMATION; CONTRACTION;
Keywords:
endothelin-1; endothelin-converting enzyme inhibitors; endothelin receptors; influenza A virus; lung; tracheal smooth muscle;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Henry, PJ Univ Western Australia, Dept Pharmacol, Nedlands, WA 6907, Australia Univ Western Australia Nedlands WA Australia 6907 07, Australia
Citazione:
P.J. Henry et al., "The role of endothelin in mediating virus-induced changes in endothelin(B)receptor density in mouse airways", EUR RESP J, 14(1), 1999, pp. 92-97

Abstract

Emerging evidence supports a mediator role for endothelin (ET)-1 in airwaydiseases including asthma. Respiratory tract viral infections, are associated with increased levels of ET and altered ET receptor density and function in murine airways. To determine whether these virus-induced effects are causally linked, perhaps involving ET-1-induced ETB receptor downregulation,the current study investigated the influence of in vivo administration of CGS 26303, an ET-converting enzyme inhibitor, on virus-induced changes in ET-content and ETB receptor density. CGS 26303 (5 mg.kg(-1)day(-1)) or placebo was administered to mice via osmotic minipumps implanted subcutaneously. Two days after implantation, mice were inoculated with influenza A/PR-8/34 virus or sham-infected, and all measurements were performed on tissue obtained on the fourth day post-inoculation. Viral infection was associated with elevated levels of immunoreactive ET and decreased densities of ETB receptors in murine airways. Both of these effects were attenuated in virus-infected mice that had received CGS 26303. Virus-induced increases in wet lung weight were also inhibited by CGS 26303. Importantly, administration of CGS 26303 had no effect on the titres of infectious virus in the lungs and similarly, viral infection had no effect onthe plasma levels of free CGS 26303. In summary, CGS 26303 inhibited the virus-induced changes in both immunoreactive endothelin content and endothelin(B) receptor density. These findings are consistent,vith the postulate that the elevated epithelial expressionof endothelin-1 during respiratory tract viral infection is a contributingfactor in the downregulation of endothelin(B) receptors in airway smooth muscle. Whether inhibitors of endothelin synthesis attenuate virus-induced exacerbations of asthma or airways hyperresponsiveness remains to be established.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 10:55:02