Effects of Ketamine on Carbachol and Epidermal Growth Factor Contraction in Rat Trachea / 대한마취과학회지

ABSTRACT

BACKGROUND: It is well known that ketamine, a dissociative anesthetic, inhibits smooth muscle contractions induced by high KCl and receptor agonists such as carbachol, histamine and endothelin. It has been reported that the inhibitory effect is mediated by a decrease in Ca2+ influx through the plasma membrane in smooth muscle. However, the mechanism of action for ketamine is not fully understood. In the present study, the effect of ketamine on Ca2+ -dependent and -independent carbachol and epidermal growth factor (EGF) contractions was investigated in rat tracheal smooth muscle. METHODS: Tracheal smooth muscle strips from Sprague-Dawley rats were mounted in an organ bath with physiological salt solution (PSS, pH 7.4, 37oC). When high KCl and carbachol (1, 10 micrometer) induced contraction and verapamil and ketamine attenuated contraction, and when EGF or carbachol alone and EGF plus carbachol in Ca2+ free media induced contration and verapamil and ketamine inhibited contration, the changes in tention of the muscle strips were measured. RESULTS: 1) Ketamine inhibited the contractions stimulated by high KCl (70 mM) and carbachol (1, 10 micrometer) in a concentration-dependent manner. The inhibitory effect was more marked in the 1 micrometer carbachol preparation than in the 10 micrometer carbachol preparation. 2) Although the contraction induced by carbachol (1 micrometer) was attenuated by verapamil (10 micrometer), a voltage-dependent Ca2+ channel blocker, the degree of inhibition was not complete, but only partial. The verapamil-insensitive portion of the contraction induced by carbachol was completely inhibited by the cumulative application of ketamine. 3) EGF (1 mg/ml), a tyrosine kinase-associated growth factor, or carbachol alone did not induce contraction in Ca2+ -free PSS (1 mM EGTA). However EGF plus carbachol contracted tracheal smooth muscle in the Ca2+ -free media and it was completely inhibited by ketamine but not by verapamil. CONCLUSIONS: These results suggest that ketamine inhibits the smooth muscle contraction including both verapamil-sensitive and -insensitive Ca2+ increments and by Ca2+ -independent contraction mechanisms.