The inhibitory effect of X537A on vascular and intestinal smooth muscle contraction.

Abstract

The effects of X537A (Lasalocid) on contractions induced in vascular and intestinal smooth muscles were examined. High K-induced sustained contractions were inhibited by X537A with an IC50 of 2.8 X 10(-6) M in rabbit aorta and 8.8 X 10(-8) M in guinea-pig Taenia coli. Changing the Ca concentration in the medium did not modify the effect of X537A. X537A also inhibited the noradrenaline-induced contraction in aorta (IC50 = 7.0 X 10(-8) M). In a solution without added glucose, the inhibitory effect of X537A on the K-induced contraction in aorta was augmented (IC50 = 1.5 X 10(-8) M). Under hypoxic conditions, the inhibitory effects of X537A on the noradrenaline-induced contractions in aorta and on the K-induced contraction in T. coli were decreased (IC50 greater than 10(-5) M and 3.2 X 10(-6) M, respectively). X537A inhibited the K-induced increase in cellular 45Ca content in aorta measured by a modified lanthanum method. However, the IC50 for 45Ca uptake (6.6 X 10(-7) M) was lower than that for K-induced contraction. In both tissues, X537A decreased the ATP content. Oxygen consumption of rat liver mitochondria was inhibited by X537A. From these results, it is concluded that the inhibitory effect of X537A on the noradrenaline-induced contraction in aorta and the K-induced contraction in T. coli, but not the K-induced contractions in aorta, may be due to the inhibition of aerobic metabolism.