Knox A J, Ajao P
Respiratory Medicine Unit, City Hospital, Nottingham, UK.
Pulm Pharmacol. 1994 Apr;7(2):99-102. doi: 10.1006/pulp.1994.1011.
We have previously shown that amiloride, an inhibitor of several cell membrane sodium exchangers and channels including Na/H exchange and Na/Ca exchange, inhibits receptor-operated contraction of bovine airway smooth muscle. However, the precise mechanism of action of amiloride is unknown. To evaluate the mechanism whereby amiloride reduces airway smooth muscle contractility, we compared the effects of amiloride with 5-N-methyl isobutyl amiloride and 5-N,N-hexamethylene amiloride, selective inhibitors of Na/H exchange, and 5-N(N-4-chlorobenzyl)-2,4-dimethyl benzamil, a selective inhibitor of Na/Ca exchange on histamine-induced contraction of bovine trachea. Unlike amiloride, none of the amiloride analogues, 5-N-methyl isobutyl amiloride (10 mumol/l), 5-N,N-hexamethylene amiloride (10 mumol/l) nor 5-N(N-4-chlorobenzyl)-2,4-dimethyl benzamil (20 mumol/l), inhibited histamine-induced contraction. Our results do not support the hypothesis that Na/H exchange or Na/Ca exchange are involved in histamine-induced contraction of airway smooth muscle.
我们之前已经表明，氨氯吡咪，一种包括钠/氢交换和钠/钙交换在内的多种细胞膜钠交换体和通道的抑制剂，能够抑制牛气道平滑肌的受体介导收缩。然而，氨氯吡咪确切的作用机制尚不清楚。为了评估氨氯吡咪降低气道平滑肌收缩性的机制，我们比较了氨氯吡咪与钠/氢交换的选择性抑制剂5-N-甲基异丁基氨氯吡咪和5-N,N-六亚甲基氨氯吡咪，以及钠/钙交换的选择性抑制剂5-N(N-4-氯苄基)-2,4-二甲基苄胺咪对组胺诱导的牛气管收缩的影响。与氨氯吡咪不同，氨氯吡咪类似物5-N-甲基异丁基氨氯吡咪（10微摩尔/升）、5-N,N-六亚甲基氨氯吡咪（10微摩尔/升）和5-N(N-4-氯苄基)-2,4-二甲基苄胺咪（20微摩尔/升）均未抑制组胺诱导的收缩。我们的结果不支持钠/氢交换或钠/钙交换参与气道平滑肌组胺诱导收缩的假说。
