Shigyo M, Aizawa H, Inoue H, Matsumoto K, Takata S, Hara N
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Eur Respir J. 1998 Jul;12(1):64-70. doi: 10.1183/09031936.98.12010064.
To clarify the protective effects of pituitary adenylate cyclase activating peptide (PACAP) on airway narrowing, we examined the effects of PACAP on smooth muscle contraction and plasma extravasation in guinea-pig airways. Smooth muscle contraction evoked by electrical field stimulation (EFS) or exogenously applied acetylcholine (ACh) or substance P (SP) was measured before and after PACAP in vitro. The effect of PACAP on airway plasma extravasation was also measured in vivo. In trachea, PACAP (10(-9) - 10(-7) M) significantly suppressed smooth muscle contraction evoked by EFS without affecting ACh sensitivity, suggesting that PACAP inhibits cholinergic neuroeffector transmission. In the main bronchi, PACAP (10(-9) - 10(-8) M) significantly suppressed the contraction evoked by EFS without affecting SP sensitivity in the presence of atropine, suggesting that PACAP inhibits SP release from excitatory nonadrenergic noncholinergic (eNANC) nerves. In animals treated with atropine and propranolol, PACAP attenuated the increase in plasma extravasation induced by electrical vagus stimulation or by SP. These results suggest that pituitary adenylate cyclase activating peptide may play a role in modulation of airway responses through inhibition of cholinergic and noncholinergic mechanisms.
为阐明垂体腺苷酸环化酶激活肽（PACAP）对气道狭窄的保护作用，我们研究了PACAP对豚鼠气道平滑肌收缩和血浆外渗的影响。在体外，于PACAP处理前后测量电场刺激（EFS）或外源性应用乙酰胆碱（ACh）或P物质（SP）诱发的平滑肌收缩。还在体内测量了PACAP对气道血浆外渗的影响。在气管中，PACAP（10^(-9) - 10^(-7) M）显著抑制EFS诱发的平滑肌收缩，而不影响ACh敏感性，提示PACAP抑制胆碱能神经效应传递。在主支气管中，在阿托品存在的情况下，PACAP（10^(-9) - 10^(-8) M）显著抑制EFS诱发的收缩，而不影响SP敏感性，提示PACAP抑制兴奋性非肾上腺素能非胆碱能（eNANC）神经释放SP。在用阿托品和普萘洛尔处理的动物中，PACAP减弱了电刺激迷走神经或SP诱导的血浆外渗增加。这些结果提示垂体腺苷酸环化酶激活肽可能通过抑制胆碱能和非胆碱能机制在气道反应调节中发挥作用。
