A submucosal mechanism of action for prostaglandin E2 on hexose absorption and metabolism in mouse intestine.
1. The involvement of prostaglandin E2 (PGE2) in hexose absorption and metabolism was studied in mouse small intestinal villus cells. 2. Phlorizin-sensitive, Na(+)-dependent alpha-methyl-D-glucoside (alpha-MG) uptake (0.8 mM) during 2 min cell incubations (37 degrees C) was 74 +/- 4 nmol (mg protein)-1. Maximal uptake was 110 +/- 8 nmol (mg protein)-1, representing an accumulation of 50-fold. Metabolism of D-glucose (5 mM) to L-lactate was 38 nmol min-1 (mg protein)-1. 3. Incubation of isolated cells with indomethacin or PGE2 did not affect alpha-MG uptake or D-glucose metabolism. By including indomethacin during cell isolation from whole intestine, alpha-MG uptake was inhibited dose dependently (50-250 microM) by up to 70% (P < 0.001). PGE2 present during both isolation and incubation inhibited by 85% (P < 0.001) at 1 microM and by 27% (P < 0.05) at 0.1 microM, with no effect at lower concentrations. alpha-MG uptake was reduced to 38% (P < 0.01) when 1 microM-PGE2 and 250 microM-indomethacin were presented in combination. When present during cell isolation and incubation, 1 microM-PGE2 inhibited lactate production by 24% (P < 0.05), except when present in combination with 250 microM-indomethacin. Indomethacin, itself, had no effect on lactate production. 4. A submucosal mechanism is proposed to account for the observed inhibitory effects of PGE2 on brush-border uptake of alpha-MG and cellular lactate production. Indomethacin appears to exert not only an effect of its own, possibly via PG-independent actions within the submucosa, but at high concentrations also disrupts the effects of exogenously applied PGE2.
Dempster
J A
JA
Department of Biology, University of York, Heslington.
Kellett
G L
GL
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008297:Male; D008757:Methylglucosides / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C
D006601:Hexoses; D007773:Lactates; D008757:Methylglucosides; D019344:Lactic Acid; C027020:methylglucoside; D005947:Glucose; D015232:Dinoprostone