title: Augmented PDBu-mediated contraction of bronchial smooth muscle of mice with antigen-induced airway hyperresponsiveness.
abstract: To explore the role of protein kinase C (PKC) in the augmented bronchial smooth muscle (BSM) contraction observed in the antigen-induced airway hyperresponsive (AHR) mice, the effects of a PKC activator, phorbol 12,13-dibutylate (PDBu), on BSM contraction were compared between the AHR and control mice. Actively sensitized mice were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge the isometrical contractions of the BSMs were measured. The BSM contraction induced by acetylcholine, but not high K(+) depolarization, was significantly augmented in the AHR mice. In BSMs of control mice, PDBu caused a significant increase in tension when the tissues were precontracted with high K(+), although PDBu itself had no effect on basal tone. The PDBu-mediated contraction was markedly augmented in BSMs of the AHR mice. These findings suggest that an increase in the PKC-mediated signaling is involved in the augmented contraction of BSMs in the antigen-induced AHR mice.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, Japan. sakai@hoshi.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D002273:Carcinogens; D015240:Phorbol 12,13-Dibutyrate; D010047:Ovalbumin; D011493:Protein Kinase C; D000109:Acetylcholine