Inhibitory effect of X 537A on vascular and intestinal smooth muscles

Abstract

Inhibitory effects of an antibiotic ionophore, X 537A, on smooth muscle contractions were examined. In rabbit aorta, isosmotic 65.4mM K-induced sustained contraction was inhibited by X 537A (IC50=2.8X10-6M). The K-induced contraction was more effectively inhibited by X 537A in the absence of added glucose (IC50 = 1.5X10-8M). Norepinephrine (10-6M)-induced sustained contraction in aorta was inhibited by X 537A in norma! solution (IC 50=8X10-8M), but not in the presence of 40mM glucose in hypoxia. In guinea-pig taenia coli, hyperosmotic 45.4mM K-induced sustained contraction was inhibited by X 537A (IC50=8.8X10-8M), while the K-induced initial transient contraction was less sensitive to X 537A. Hypoxia and high concentration of glucose decreased the inhibitory effect of X 537A on the K-induced sustained contraction in taenia coli. In both tissues, ATP contents were decreased by X 537A in high K solutions. X 537A also inhibited the oxygen consumption of rat liver mitochondria initiated by ADP and succinate. In aorta, the increase in celluar 4.5Ca content by K (measured by a modified lanthanum method) was inhibited by X 537A at the concentration lower than that needed to inhibit the K-induced contraction. From these results, it was concluded that X 537A inhibits the smooth muscle contractions mainly by an inhibition of aerobic metabolism.