Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma.

Yoshihiko Chiba, Chihiro Ueda, Naoko Kohno, Michio Yamashita, Yui Miyakawa, Yusuke Ando, Wataru Suto, Takahiro Hirabayashi, Fumiko Takenoya, Ichiro Takasaki, Junzo Kamei, Hiroyasu Sakai, Seiji Shioda

American journal of physiology. Lung cellular and molecular physiology 2020 Nov 01

filter terms:

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of airway hyperresponsiveness (AHR), 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 downregulation of its binding partner PAC1 receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

Citation

Yoshihiko Chiba, Chihiro Ueda, Naoko Kohno, Michio Yamashita, Yui Miyakawa, Yusuke Ando, Wataru Suto, Takahiro Hirabayashi, Fumiko Takenoya, Ichiro Takasaki, Junzo Kamei, Hiroyasu Sakai, Seiji Shioda. Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma. American journal of physiology. Lung cellular and molecular physiology. 2020 Nov 01;319(5):L786-L793