Oxidant-stimulated chloride secretion in rat jejunum in vitro is mediated by eicosanoids

Specific effects of the cytotoxic secondary lipid oxidation product, 4- hydroxynonenal (10(-8) - 10(-4) M), on intact sheets of rat jejunum were measured as changes in short circuit current (DeltaI(sc)) following cumulative addition to either the mucosal or serosal side, using the analogous aldehyde, nonenal, as reference. 4- Hydroxynonenal stimulated I-sc from the serosal side (maximal DeltaI(sc) = 27:2 +/- 3:5 muA/cm(2), mean +/- SEM, N = 32) while nonenal stimulated Isc primarily from the mucosal side (maximal DeltaI(sc) = 16:2 +/- 3:4 muA/ cm(2), N = 20). Inhibition by 100 muM bumetanide (4- hydroxynonenal: 88.9 +/- 3.0%, N = 6, p < 0:05, nonenal: 69.3 +/- 2.9%, N = 6, P < 0:05) indicated chloride secretion. Nonenal- induced DeltaI(sc) was inhibited (72.5 +/- 1.2%, N = 8, P < 0:05) by a combination of nordihydroguaiaretic acid (100 &mu;M) and piroxicam (10 &mu;M), while 4- hydroxynonenal- induced &UDelta;I-sc, was abolished by piroxicam (N = 8, P < 0:001) and inhibited by 1 muM tetrodotoxin (69.8 +/- 9.7%, N = 6, P < 0:001). These data indicate that 4- hydroxynonenal stimulates chloride secretion mediated by prostaglandins and the enteric nervous system. The site of action (serosal) being opposite to the reference aldehyde.