Matsumoto K, Aizawa H, Inoue R, Hamano S, Ikeda S, Xie Z, Hirata M, Hara N, Ito Y
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Am J Respir Cell Mol Biol. 1994 Mar;10(3):322-30. doi: 10.1165/ajrcmb.10.3.8117450.
We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.
我们研究了培养的上皮细胞及其上清液对犬气管和细支气管平滑肌细胞静息膜电位以及兴奋性神经效应传递的影响。无黏膜气管平滑肌细胞的平均静息膜电位为-59.5±1.5 mV（±标准差）。应用培养的上皮细胞（>2.5×10⁵个细胞/ml）可使膜超极化，导致电位为-64.5±1.7 mV。培养的上皮细胞的上清液也使无黏膜气管平滑肌细胞的静息膜电位增加了4至9 mV。这些超极化作用不受吲哚美辛（10⁻⁵ M）、L-硝基精氨酸（10⁻⁵ M）或氧合血红蛋白（10⁻⁵ M）的影响，但被格列本脲（10⁻⁶ M）抑制。培养的上皮细胞的上清液完全或部分抑制了去上皮细支气管对电场刺激的收缩反应，并抑制了电场刺激诱发的气管平滑肌兴奋性接头电位的幅度。吲哚美辛可防止上清液对抽搐收缩幅度和兴奋性接头电位的抑制作用，并显著抑制上清液相关的兴奋性神经效应传递抑制。此外，吲哚美辛与脂氧合酶抑制剂AA861一起可完全抑制这种作用。我们的研究结果表明，培养的气道上皮细胞可自发释放至少两种因子。一种因子选择性地调节静息膜电位，另一种则抑制兴奋性神经效应传递。
