Satoh H, Lou Y P, Lundberg J M
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Eur J Pharmacol. 1993 Jun 4;236(3):367-72. doi: 10.1016/0014-2999(93)90473-u.
We have examined the effects of capsazepine, a selective capsaicin antagonist, and SR 48968, a selective NK2 receptor antagonist, on citric acid inhalation-induced bronchoconstriction in guinea-pigs. Simultaneous inhalation of capsazepine (10 microM) significantly inhibited (by 85%) the bronchoconstriction induced by inhaled citric acid (0.4 M) but not that induced by histamine (2 mM). In capsaicin-pretreated (50 mg/kg s.c. 3 weeks earlier) guinea-pigs, citric acid failed to cause any bronchoconstriction, while the effect of histamine was uninfluenced. Furthermore, citric acid inhalation-induced bronchoconstriction was also markedly inhibited (by 65%) after pretreatment with SR 48968 (0.3 mg/kg i.v.). SR 48968 blocked the bronchoconstriction but not the hypotension evoked by neurokinin A. Therefore, these results suggest that inhalation of a low-pH solution such as citric acid can stimulate sensory neurons through a mechanism similar to that for capsaicin with regard to sensitivity to capsazepine. Tachykinins such as neurokinin A are then locally released from the terminals of sensory nerves and cause bronchoconstriction, mainly by NK2 receptor mechanisms.
我们研究了选择性辣椒素拮抗剂辣椒平以及选择性NK2受体拮抗剂SR 48968对柠檬酸吸入诱发的豚鼠支气管收缩的影响。同时吸入辣椒平（10微摩尔）可显著抑制（85%）吸入柠檬酸（0.4摩尔）诱发的支气管收缩，但对组胺（2毫摩尔）诱发的支气管收缩无抑制作用。在预先经辣椒素处理（3周前皮下注射50毫克/千克）的豚鼠中，柠檬酸未能引起任何支气管收缩，而组胺的作用未受影响。此外，预先用SR 48968（静脉注射0.3毫克/千克）处理后，柠檬酸吸入诱发的支气管收缩也受到显著抑制（65%）。SR 48968可阻断支气管收缩，但不阻断神经激肽A诱发的低血压。因此，这些结果表明，吸入低pH溶液如柠檬酸可通过一种与辣椒素类似的机制刺激感觉神经元，这种机制在对辣椒平的敏感性方面与辣椒素相似。然后，速激肽如神经激肽A从感觉神经末梢局部释放，主要通过NK2受体机制引起支气管收缩。
