EFFECT OF NORDIHYDROGUAIARETIC ACID ON GLUCOSE-ABSORPTION, METABOLISM AND (NA+ + K+)-ATPASE ACTIVITY IN RAT JEJUNUM

A regulatory role of endogenously synthesized eicosanoids on the absorption, transmural transport and metabolism of glucose in perfused, isolated loops of jejunum in vitro was investigated using the lipoxygenase/cyclooxygenase inhibitor, nordihydroguaiaretic acid (NDGA). NDGA diminished glucose absorption over the range 100-500 muM: maximal inhibition at 500 muM NDGA was 52 +/- 9 and 64 +/- 9% (mean +/- SE, P < 0.001) for jejuna from fed rats and rats maintained on glucose water for 48 hr, respectively. In each instance, transmural transport was effectively abolished. The vectorial disposition of lactate release was also changed such that the ratio of luminal to serosal production was increased from 0.19 +/- 0.02 to 1.72 +/- 0.12 (P < 0.001) in fed rats, indicating inhibition of the Na+ pump. NDGA inhibited (Na+ + K+)-ATPase activity in whole mucosal homogenates with a concentration dependence similar to that observed for glucose absorption. However, NDGA also inhibited Mg2+-ATPase activity in whole homogenates and purified rabbit skeletal muscle phosphofructokinase under the same conditions. The results are discussed in terms of the dissipation of the transmembrane Na+ gradient via direct inhibition of the (Na+ + K+)-ATPase by NDGA. Inhibition of the AtPase precludes the use of NDGA as a suitable drug with which to investigate the role of endogenously synthesized eicosanoids in the regulation of intestinal function.