THE EFFECT OF SODIUM FLUOROACETATE ON THE CONTRACTILITY AND METABOLISM OF INTESTINAL SMOOTH MUSCLE

¹ Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri

1. The effect of sodium fluoroacetate on the contractile activity of the longitudinal smooth muscle of segments of rabbit small intestine suspended in Lrebs-bicarbonate solution was studied under various conditions.

2. Under aerobic conditions in the presence of glucose, added either at the beginning of the experiment or after depletion of the endogenous substrate of the longitudinal muscle, contractile activity of segments from the upper small intestine was maximally inhibited by fluoroacetate to the extent of 50 per cent to 85 per cent (average, 65 per cent). Activity of ileal segments was inhibited somewhat less markedly. The initial inhibition in the presence of glucose was followed by the development of a contraction pattern characterized by slow, and often exaggerated, rhythmic fluctuations in tone.

3. Under aerobic conditions, contractile activity maintained by acetate, pyruvate or caprylate (added after depletion of endogenous substrate) was inhibited completely by fluoroacetate.

4. The relatively weak contractile activity exhibited under anaerobic conditions in the presence of glucose was not affected by fluoroacetate.

5. The inhibitory effect of fluoroacetate on aerobic contractile activity could not be removed by repeated washing of the intestinal segment with fluoroacetate-free medium. However, when fluoroacetate was added during a period of anoxia, and the intestinal segment was washed under anaerobic conditions later in the same period, the subsequent reintroduction of oxygen restored a normal uninhibited aerobic contraction pattern.

6. Fluoroacetate markedly inhibited the oxygen consumption of isolated rabbit intestinal smooth muscle in the presence of glucose, but did not affect the anaerobic glycolysis.

7. The experimental results may be explained by the hypothesis that fluoroacetate inhibits oxidative metabolism in smooth muscle somewhere below the level of acetate, at a stage in the common pathway for the oxidation of acetate, fatty acids, pyruvate and glucose. In addition, it appears that inhibition is not produced until a reaction, limited to aerobic conditions, occurs between the added fluoroacetate and some constituent of the smooth muscle.

8. A "reversal" of the usual effects of acetylcholine and epinephrine was sometimes observed with intestinal segments poisoned with fluoroacetate.