Effects of Folic Acid and Pyrimethamine, a Dihydrofolate Reductase Inhibitor, on Intestinal Absorption of Folates in Rats
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概要
- 論文の詳細を見る
Oral co-administration of folic acid (pteroylglutamic acid, PteGlu) potentiates the decrease of plasma 5-methyltetrahydrofolic acid (5-CH<SUB>3</SUB>-H<SUB>4</SUB>PteGlu) concentration induced by pyrimethamine (PYR) in rats. To clarify the mechanisms of this potentiated decrease, we examined the effects of PteGlu and PYR on intestinal absorption of folates in rat jejunum loops, because plasma 5-CH<SUB>3-H</SUB>4PteGlu concentration is maintained by enterohepatic circulation of folates. The intestinal absorption of 5-[<SUP>14</SUP>C]CH<SUB>3</SUB>-H<SUB>4</SUB>PteGlu was inhibited by PteGlu, but not by PYR. The absorption of [<SUP>3</SUP>H]PteGlu was inhibited by reduced folates that exist in bile. These findings indicate that PteGlu competes with the bile reduced folates for the intestinal transport system. The bile secretion of reduced folates was also examined to observe the conversion of absorbed PteGlu to reduced folates in the liver in the presence of PYR. The bile secretion of reduced folates increased drastically after the administration of PteGlu alone, but not after the administration of PteGlu with PYR. These facts suggest that the absorbed PteGlu was not converted to reduced folates in the liver due to PYR. In conclusion, the potentiated decrease of plasma 5-CH<SUB>3</SUB>-H<SUB>4</SUB>PteGlu concentration must have resulted from a combination of the following two factors: the inhibition of reabsorption of bile reduced folates by PteGlu and the inhibition of PteGlu conversion to reduced folates in the liver by PYR.
- 社団法人 日本薬理学会の論文
- 1995-10-01
著者
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Kudo Gen
Department Of Radiology Fujita Health University
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Kudo Gen
Department Of Veterinary Medicine Faculty Of Agriculture Tokyo University Of Agriculture And Technol
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Shimoda Minoru
Department Of Veterinary Medicine Faculty Of Agriculture Tokyo University Of Agriculture And Technol
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KOKUE Ei-ichi
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Techn
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OHGUSHI Naofumi
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Techn
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Ohgushi Naofumi
Department Of Veterinary Medicine Faculty Of Agriculture Tokyo University Of Agriculture And Technol
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Kokue Ei-ichi
Department Of Veterinary Medicine Faculty Of Agriculture Tokyo University Of Agriculture And Technol
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Kokue Ei-ichi
Department Of Veterinary Medicine Faculty Of Agriculture Tokyo University Of Agriculture And Technol
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