Ellis J L, Undem B J
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.
J Pharmacol Exp Ther. 1992 Aug;262(2):646-53.
Nonadrenergic, noncholinergic contractions were elicited by electrical field stimulation (EFS) (2 Hz, 1 msec, 12 V for 15 sec) of the distal aspect of guinea pig trachea pretreated with atropine (1 microM), propranolol (1 microM) and indomethacin (3 microM). The contractions were abolished by pretreatment with the sensory C-fiber toxin capsaicin or by a combination of the neurokinin (NK)1 receptor antagonist, CP 96,345 (0.1 microM), and the NK2 receptor antagonist, MEN 10376 (3 microM), and were markedly attenuated by tetrodotoxin. In animals actively sensitized to ovalbumin, the addition of threshold concentrations of antigen markedly increased the noncholinergic contractile responses to EFS (approximately 3- to 6-fold). This potentiation was long lasting, persisting virtually unchanged for 60 min, whereas the antigen-induced contractions were shorter lived, usually lasting less than 30 min. The ovalbumin-induced potentiation of the neuronal response was not observed in tissues pretreated with capsaicin or treated with tetrodotoxin. This antigen-induced potentiation of capsaicin-sensitive, EFS-induced contractions was not mimicked by serotonin or prostaglandin D2. However, it was mimicked by histamine. Moreover, the histamine H1 receptor antagonist pyrilamine (0.3 microM) reversed the potentiation elicited by ovalbumin. The effect of ovalbumin challenge was also examined on the distal trachea with the right vagus nerve intact. Noncholinergic contractions to EFS and vagus nerve stimulation were enhanced equally by threshold concentrations of antigen. The results support the hypothesis that antigen challenge releases histamine which acts via H1 receptors to enhance noncholinergic contractions due to the release of tachykinins from capsaicin-sensitive fibers in the guinea pig trachea.
在用阿托品（1微摩尔）、普萘洛尔（1微摩尔）和吲哚美辛（3微摩尔）预处理的豚鼠气管远端，通过电场刺激（EFS）（2赫兹，1毫秒，12伏，持续15秒）诱发非肾上腺素能、非胆碱能收缩。用感觉C纤维毒素辣椒素预处理或用神经激肽（NK）1受体拮抗剂CP 96,345（0.1微摩尔）和NK2受体拮抗剂MEN 10376（3微摩尔）联合处理可消除收缩，河豚毒素可使其明显减弱。在对卵清蛋白主动致敏的动物中，加入阈浓度的抗原可显著增加对EFS的非胆碱能收缩反应（约3至6倍）。这种增强作用持续时间长，在60分钟内基本保持不变，而抗原诱导的收缩持续时间较短，通常不到30分钟。在用辣椒素预处理或用河豚毒素处理的组织中未观察到卵清蛋白诱导的神经元反应增强。5-羟色胺或前列腺素D2不能模拟这种抗原诱导的对辣椒素敏感的、EFS诱导的收缩增强作用。然而，组胺可以模拟。此外，组胺H1受体拮抗剂吡苄明（0.3微摩尔）可逆转卵清蛋白引起的增强作用。还研究了卵清蛋白激发对右侧迷走神经完整的气管远端的影响。阈浓度的抗原同样增强了对EFS和迷走神经刺激的非胆碱能收缩。结果支持这样的假说：抗原激发释放组胺，组胺通过H1受体起作用，由于豚鼠气管中辣椒素敏感纤维释放速激肽而增强非胆碱能收缩。
