Modulation of the reactivity of the guinea-pig isolated trachealis by respiratory epithelium: effects of cooling.
Br J Pharmacol 1990 Feb; 99(2):369-373
The effects of temperature on the responses of intact and epithelium denuded guinea-pig tracheal strips to methacholine were examined. Intact tracheal strips prepared from male English-short-haired- guinea-pigs or tracheal strips with the respiratory epithelium removed (denuded strips) were placed in an isometric force apparatus and incubated with modified Krebs-Henseleit buffer containing 0 to 10(-3) molar (M) methacholine-chloride at 37 or 22 degrees-C in the presence or absence of 1 micromolar (microM) indomethacin or 1 to 10microM ouabain. The effects on contractile force induced by methacholine were determined. A similar experiment was performed in which the temperature was abruptly changed from 37 to 22 degrees or from 22 to 37 degrees. Removal of the epithelium increased tracheal responsiveness to methacholine by 3.6 fold compared to the control value at 37 degrees. Sensitivity to methacholine at 22 degrees was decreased by a factor of 6. Sensitivity to methacholine of intact preparations was not affected by temperature. The maximum contractile forced induced by methacholine at 37 degrees was not affected by epithelium removal. The maximum force in intact strips at 22 degrees was 60% higher than at 37 degrees. Epithelium removal reduced the maximum force by 39%. Indomethacin decreased the spontaneous contractility of intact and denuded tracheal strips at 37 degrees, but not at 22 degrees. Indomethacin increased the sensitivity of intact strips to methacholine at 37 degrees. The increase was not enhanced by removing the epithelium. Indomethacin had no effect on the response to methacholine at 22 degrees. Abruptly decreasing the temperature of intact or denuded tracheal strips from 37 to 22 degrees had no effect on methacholine responsiveness. Abruptly increasing the temperature from 22 to 37 degrees decreased the response to methacholine. The decrease was greater in intact strips and was followed by a contraction. Indomethacin had no effect. Ouabain at 1microM had no effect on intact preparations but induced contractions in denuded strips. Ouabain at 10microM inhibited the relaxation of intact strips. The authors conclude that the modulatory effect of tracheal respiratory epithelium on methacholine responsiveness is temperature dependent and involves stimulation of the sodium/potassium pump.
NIOSH-Author; In-vitro-studies; Muscle-tissue; Drugs; Thermal-effects; Muscle-contraction; Respiratory-system-disorders; Physiological-response; Laboratory-animals; In-vitro-studies
Jeffrey S. Fedan, Physiology Section, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, 944 Chestnut Ridge Road, Morgantown, WV 26505, U.S.A.
British Journal of Pharmacology