Mechanism of cooling-induced relaxation in the isolated guinea-pig trachea.
In this study, we explored the possible mechanism of cooling-induced relaxation of the isolated guinea-pig trachea. A rapid cooling (-4 degrees C/min) from 37 +/- 0.5 degree C to 25 +/- 0.5 degree C induced a transient and small contraction followed by a sustained cooling-relaxation. This relaxation was not blocked by propranolol or tetrodotoxin. Various concentrations of four contractile agonists (histamine, carbachol, 5-HT and ryanodine) all enhanced cooling-relaxation in a concentration-dependent manner which correlated well with their increase in the developed muscular tension, suggesting an inherent counterbalance between cooling-relaxation and the bronchoconstriction. Treating with either indomethacin or nordihydroguaiaretic acid (NDGA) did not affect the contractile properties of histamine, carbachol and 5-HT except ryanodine, but reversed cooling-relaxation into sustained cooling-contraction. Indomethacin partially inhibited but NDGA abolished cooling-relaxation induced by ryanodine. Moreover, ryanodine, but not the other three contractile agonists, could antagonize indomethacin in inducing cooling-contractions by various agonists. From above findings, we can conclude that eicosanoids including prostaglandins particularly leukotrienes, which would be produced by the elevated Ca(2+)-release from the ryanodine sensitive Ca(2+)-store, play prominent roles in inducing cooling-relaxation.
Chou
D S
DS
Department of Pharmacology, Taipei Medical College, Taiwan.
Chen
T F
TF
Lin-Shiau
S Y
SY
D000818:Animals; D003080:Cold Temperature; D006168:Guinea Pigs; D006358:Hot Temperature; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction; D009126:Muscle Relaxation; D011433:Propranolol / Q000494:pharmacology; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D013779:Tetrodotoxin; D009637:Masoprocol; D011433:Propranolol; D007213:Indomethacin