Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM is unknown. The current study examined the hypothesis that relaxation induced by PACAP is reduced in bronchial smooth muscle (BSM) of allergic asthma. The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated. Tension study showed a BSM hyperresponsiveness to acetylcholine in the OA-challenged mice. Both quantitative RT-PCR and immunoblot analyses revealed a significant decrease in PAC₁ receptor expression in BSMs of the diseased mice. Accordingly, in the antigen-challenged group, the PACAP-induced PAC₁ receptor-mediated BSM relaxation was significantly attenuated, whereas the relaxation induced by vasoactive intestinal polypeptide was not changed. These findings suggest that the relaxation induced by PACAP is impaired in BSMs of experimental asthma due to a down-regulation of its binding partner PAC₁receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

中文翻译：

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垂体腺苷酸环化酶激活多肽在实验性哮喘支气管平滑肌中引起的松弛反应的减弱。

支气管舒张压通过气道平滑肌（ASM）的收缩和松弛来调节。ASM松弛减弱可能是气道高反应性的原因，这是支气管哮喘的特征。垂体腺苷酸环化酶激活多肽（PACAP）是导致ASM松弛的介体。迄今为止，尚不清楚哮喘ASM中PACAP反应是否改变。当前的研究检验了以下假设：过敏性哮喘的支气管平滑肌（PAM）减少了PACAP引起的松弛。卵清蛋白（OA）致敏的小鼠反复受到气雾化OA的攻击，以诱发哮喘反应。最后一次抗原攻击后二十四小时，分离出主要的支气管平滑肌（BSM）组织。张力研究表明，OA挑战小鼠的BSM对乙酰胆碱反应过度。定量RT-PCR和免疫印迹分析均显示PAC显着降低在患病小鼠的BSM中有_1种受体表达。因此，在抗原挑战组中，PACAP诱导的PAC ₁受体介导的BSM松弛明显减弱，而血管活性肠多肽诱导的松弛没有改变。这些发现表明，PACAP诱导的松弛在实验性哮喘的BSM中受损，这是由于其结合伴侣PAC ₁受体的下调所致。BSM对PACAP的反应性受损可能会导致哮喘的AHR。