NEUTRAL ENDOPEPTIDASE MODULATES ENDOTHELIN-1-INDUCED AIRWAY SMOOTH-MUSCLE CONTRACTION IN GUINEA-PIG TRACHEA

被引:17
作者
DIMARIA, GU
KATAYAMA, M
BORSON, DB
NADEL, JA
机构
[1] UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143
关键词
ENKEPHALINASE; PEPTIDE; PEPTIDASE; TACHYKININ METABOLISM;
D O I
10.1016/0167-0115(92)90535-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study was designed to evaluate the role of neutral endopeptidase (NEP) in modulating the airway smooth muscle contraction induced by endothelin-1 in isolated segments of guinea-pig trachea. Endothelin-1 (10(-9)-10(-6) M) produced a concentration-dependent contraction that reached a maximum by 30 min. The NEP inhibitor leucine-thiorphan (10(-5) M) significantly increased the contractile response to endothelin-1. The addition of leucine-thiorphan to tracheal segments precontracted by 10(-9) and 10(-8) M endothelin-1 increased isometric tension by 181 +/- 65% (mean +/- 1 S.E.M.; P<0.05) and by 138 +/- 49% (P<0.05), respectively. In contrast, the kininase II inhibitor captopril and the peptidase inhibitors leupeptin and bestatin had no effect. Preincubation of endothelin-1 with 1-mu-g recombinant human NEP decreased the contractile activity of endothelin-1 by 72 +/- 9%, whereas no effect was observed using heat-inactivated NEP. We conclude that NEP modulates endothelin-induced contraction of airway smooth muscle in the guinea-pig trachea.
引用
收藏
页码:137 / 145
页数:9
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