Regulation of Na+-dependent sugar transport in intestinal epithelial cells by exogenous ATP

Exogenous ATP (1 mM) exerts a dramatic biphasic effect on the accumulation of 100 micro M 3-O-methylglucose by isolated intestinal epithelial cells. The initial effect ensues approximately 15 s after exposure and inhibits 80% of the undirectional sugar influx. Cellular phosphatases totally degrade the added ATP within a period of 20 min leading to a reactivation of transport capability. The cells exposed to ATP ultimately establish a concentration gradient of sugar about twice that observed for control cells. Pyrophosphate (10 mM) delays the degradation of added ATP and prolongs the interval of transport inhibition. The late effect of gradient enhancement is still observed. No other nucleoside triphosphate induces the early inhibition of transport, but ADP is approximately two-thirds as effective as ATP. AMP and other molecules containing the adenine ring system can cause the late effect of gradient enhancement without causing an early transport inhibition. Because rotenone-treated ATP-depleted cells also show an ATP-induced inhibition of sugar influx, it seems likely that the early effect represents a direct modification of carrier capability rather than an effect mediated via an alteration of cellular energetics.