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

A regulatory role of endogenously synthesized eicosanoids on the absor ption, transmural transport and metabolism of glucose in perfused, iso lated loops of jejunum in vitro was investigated using the lipoxygenas e/cyclooxygenase inhibitor, nordihydroguaiaretic acid (NDGA). NDGA dim inished glucose absorption over the range 100-500 muM: maximal inhibit ion 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 effectiv ely abolished. The vectorial disposition of lactate release was also c hanged such that the ratio of luminal to serosal production was increa sed from 0.19 +/- 0.02 to 1.72 +/- 0.12 (P < 0.001) in fed rats, indic ating inhibition of the Na+ pump. NDGA inhibited (Na+ + K+)-ATPase act ivity in whole mucosal homogenates with a concentration dependence sim ilar to that observed for glucose absorption. However, NDGA also inhib ited Mg2+-ATPase activity in whole homogenates and purified rabbit ske letal muscle phosphofructokinase under the same conditions. The result s are discussed in terms of the dissipation of the transmembrane Na+ g radient via direct inhibition of the (Na+ + K+)-ATPase by NDGA. Inhibi tion of the AtPase precludes the use of NDGA as a suitable drug with w hich to investigate the role of endogenously synthesized eicosanoids i n the regulation of intestinal function.