Metabolism of absorbed glucose in mouse jejunum: influence of arachidonic acid, non-steroidal anti-inflammatory drugs and eicosanoids.
The involvement of arachidonic acid and eicosanoids in glucose absorption and metabolism was investigated in isolated mouse jejunum. Characteristics of glucose absorption and its metabolic fate are reported. Reduction in the dietary precursor of arachidonic acid, linoleic acid, and inhibition of phospholipid hydrolysis with mepacrine reduced glucose absorption with no effect on metabolism, although mepacrine increased the proportion of luminal to serosal lactate release. Bradykinin and n-FMLP enhanced metabolism by 2.1- and 2.4-fold, respectively, both reducing the percentage of metabolised glucose converted to lactate, while neither influenced absorption. Both indomethacin and NDGA decreased absorption and enhanced metabolism. The percentage of metabolised glucose converted to lactate decreased and the ratio of luminal to serosal lactate release was unchanged. In the absence of inhibitors, PGE2 (5 microM) decreased absorption by 28%, metabolism by 24% and total lactate production by 32% and LTB4 (20 nM) increased only absorption by 32%. PGE2 release into the perfusates was predominantly serosal (1-10 nM) and was inhibited by indomethacin. PGE2 could not reverse the indomethacin-induced decrease in absorption, but reversed the enhancement of metabolism by 89% and total lactate production by 60%. In conclusion, while the specificity of the drug-related absorptive effects remain unclear, alterations in the utilisation of the absorbed glucose via drug-induced changes in arachidonic acid synthesis and metabolism are apparent. Furthermore, exogenous PGE2 may protect against the effects of indomethacin and itself reduces active glucose absorption, the metabolism of the absorbed glucose and the amount of lactate formed.
Dempster
J A
JA
Department of Biology, University of York, Heslington, UK.
Kellett
G L
GL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; D010740:Phospholipases; D011796:Quinacrine; D005947:Glucose; D007213:Indomethacin