Intestinal transport of beta-thioglycosides by Na+/glucose cotransporter.
Intestinal metabolism and transport of p-nitrophenyl beta-D-thioglucoside (p-NPbetaSglc) and p-nitrophenyl beta-D-thiogalactoside (p-NPbetaSgal) by the Na+/glucose cotransporter were studied in excised small intestine of the rat. p-NPbetaSglc and p-NPbetaSgal were stable enough on the mucosal side to be transported to the serosal side. Transport of p-NPbetaSglc was inhibited in the presence of phloridzin (a Na+/glucose cotransporter inhibitor), glucose, or 3-O-methylglucose (3-OMG). p-NPbetaSglc transport was dependent on Na+ concentration in a sigmoidal manner. The activation energy for transport was 19.4 kcal mol(-1). The distribution of transport activity of p-NPbetaSglc in each region of the small intestine correlated well with that of 3-OMG. These results indicate that p-NPbetaSglc is transported by the Na+/glucose cotransporter in small intestine. The order of turnover rate for glycoside transport by Na+/glucose cotransporter was 3-OMG > p-nitrophenyl beta-O-glucoside > p-NPbetaSglc > p-NPbetaSgal, indicating that the presence of a galactose moiety and a sulphur between the monosaccharide moiety and aglycone decreases the turnover rate of the Na+/glucose cotransporter in the transport of glycosides. In an inhibition study using stable p-NPbetaSglc as a Na+/glucose cotransporter-transportable marker glucoside, it was also shown that the Na+/glucose cotransporter recognized several types of glycosides. In conclusion, displacement of the oxygen at carbon C-1 of glucose by sulphur in thioglycosides decreases the turnover rate of the Na+/glucose cotransporter, but thioglycosides are stable in the small intestine and are transported by the Na+/glucose cotransporter.
Mizuma
T
T
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. mizuma@ps.toyaku.ac.jp
Hagi
K
K
Awazu
S
S
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000494:pharmacology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013862:Thiogalactosides / Q000493:pharmacokinetics; D013863:Thioglucosides / Q000493:pharmacokinetics; D013865:Thioglycosides / Q000493:pharmacokinetics*; D014020:Tissue Extracts / Q000737:chemistry
D006027:Glycosides; D009004:Monosaccharide Transport Proteins; D013862:Thiogalactosides; D013863:Thioglucosides; D013865:Thioglycosides; D014020:Tissue Extracts; D019325:3-O-Methylglucose; D012964:Sodium; D010695:Phlorhizin; D019297:2,4-Dinitrophenol