Pharmacological studies on the active factors derived from airway epithelial cells.

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Airway epithelial cells do not simply act as diffusion barriers against airway stimulating substances such as toxic gases or antigens, but play an important role in regulation of the airway muscle tone by rekeasing multiple active factors. Namely, airway epitelial cells release more than two factors, one of which inhibits excitatory neuro-effector tranamission and an other which modulates the resting membrane potential of the airway smooth muscle cells. To identify these factors we cultured airway epithelial cells and used the cultuured supernatants. Cultured supernatants completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulation and suppressed the excitatory junction potentials. Cultured epithelial cells produce prostaglandins, and exogenously applied PGE_2 inhibits excitatory neuro-effector transmission presynaptically in the dog trachea and bronchioles. Therefore we radioimmunoassayd the amounts of PGE_2 in the super … More natants, which ranged between 3.1-23.8ng/ml. A high concentration of PGE_2 in the supernatant was associated with aboliton of the twitch contraction. Indomethacin, which suppresses the synthesis of PGE_2 in the suprenatants, prevented the inhibitory effect of supernatants on the twitch contractions and excitatoty junction potentials. Thus we concluded that one of the factors which is released from the airway epithelial cells and inhibits excitatory neuro-effector transmission is PGE_2. In an attempt to identify the epithelium derived hyperpolarizing factor (EpDHF) , we freeze-dried the supernatants and then applied them to Gel-filtration chromatograohy on Sephacryl S-100HR and then high-perfoamace liquid chromatofraphy on a c_<18> reversed-phase column. Hyperpolarization assay of the chromatographic fractions showed that active factors eluted in peaks coincided with low molecular weights (10-20 KD). Enzymatic treatment with proteolytic enzymes of the HPLC-purified active fraction resuletd in the abolition of hyperpolarizing activity.The results suggest that the active factor (EpDHF) 1 that was present in the cultured epithelial supenatants was a peptide in nature. Less