Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells.
To determine the effect of mediators released from cultured canine bronchial epithelial cells on contraction of canine tracheal smooth muscle, we treated smooth muscle strips with piperazine-N,N'-bis(2-ethanesulfonic acid) buffer "conditioned" by 5 h incubation with cultures of 4- to 5-day-old cultured epithelial cells. Pretreatment of tracheal smooth muscle with conditioned buffer for 5 min resulted in a significant shift to the right of the contractile dose-response curve to histamine in the range of 10(-8) to 5 x 10(-4) M. In addition, conditioned buffer induced a dose-related relaxation of the muscle precontracted by histamine (5 microM). Relaxant activity was also evident against tissues precontracted by 5-hydroxytryptamine or methacholine. Lipid extraction of conditioned buffer reduced its activity to that of the fresh buffer control. Prior treatment of the cells in culture with the cyclooxygenase inhibitor, sodium meclofenamate (4 microM), markedly reduced the relaxant effect of the conditioned buffer, whereas prior treatment with MK-886, an inhibitor of 5-lipoxygenase, did not alter relaxant activity. Analysis of prostanoids released into the buffer by epithelial cells indicated the presence of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha, the former in concentrations sufficient to account for the effect of conditioned buffer on precontracted tracheal muscle. Prostaglandin I2 appeared to have a synergistic effect on PGE2-induced relaxation. We conclude that canine bronchial epithelial cells exhibit baseline release of a relaxant lipid factor(s) that can both inhibit and reverse the contraction of tracheal smooth muscle by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Yu
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Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Hubbard
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Spannhake
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D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002021:Buffers; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000502:physiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000502:physiology*
D002021:Buffers; D015777:Eicosanoids; D011453:Prostaglandins; D012701:Serotonin; D006632:Histamine; D011464:Epoprostenol; D015232:Dinoprostone