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 (delta(I)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 delta(I)sc = 27.2 +/- 3.5 microA/cm2, mean +/- SEM, N = 32) while nonenal stimulated I(sc) primarily from the mucosal side (maximal delta(I)sc = 16.2 +/- 3.4 microA/cm2, N = 20). Inhibition by 100 microM 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 delta(I)sc was inhibited (72.5 +/- 1.2%, N = 8, P < 0.05) by a combination of nordihydroguaiaretic acid (100 microM) and piroxicam (10 microM), while 4-hydroxynonenal-induced delta(I)sc, was abolished by piroxicam (N = 8, P < 0.001) and inhibited by 1 microM 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.
Bertelsen
Lone S
LS
Centre for Advanced Food Studies Biochemistry & Nutrition, BioCentrum-DTU Technical University of Denmark, DK-2800, Denmark.
Bukhave
Klaus
K
D000447:Aldehydes / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D015777:Eicosanoids / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000502:physiology*; D007419:Intestinal Secretions / Q000187:drug effects*; D017136:Ion Transport / Q000502:physiology; D007583:Jejunum / Q000737:chemistry / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D051381:Rats
D000447:Aldehydes; D002712:Chlorides; D015777:Eicosanoids; D016877:Oxidants; D010894:Piroxicam; D009637:Masoprocol; C027576:4-hydroxy-2-nonenal