Effects of ATP-sensitive potassium channel openers on the contractile and phosphatidylinositol responses of the rat trachea.

PURPOSE: Although ATP-sensitive potassium channel openers suppress airway smooth muscle contraction, their potencies are different and the mechanisms involved are not fully understood. We examined the effects of cromakalim and Y-26763, a novel ATP-sensitive potassium channel opener, on the contractile and phosphatidylinositol responses of the rat trachea.
METHODS: Thirty-six male Wistar rats, weighing 250-350 g, were used. In the experiment on contractile response, active contraction was induced with 0.55 microM carbachol in the presence or absence of cromakalim or Y-26763. In the experiment on phosphatidylinositol response, the tracheal slices were incubated with [(3)H] myo-inositol, 0.55 microM carbachol, and cromakalim or Y-26763, and the formation of [(3)H]inositol monophosphate (IP(1)), a degradation product of phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance ( P < 0.05) was determined by analysis of variance (ANOVA).
RESULTS: Carbachol-induced tension was attenuated by both cromakalim and Y-26763, the latter displaying significantly greater potency. Carbachol-induced IP(1) accumulation was influenced neither by cromakalim nor by Y-26763.
CONCLUSION: Both cromakalim and Y-26763 have effects on airway smooth muscle relaxation. Carbachol-induced IP(1) accumulation was influenced neither by cromakalim nor by Y-26763, suggesting that phosphatidylinositol response may not be a common pathway for the effect of ATP-sensitive potassium channel openers.