Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro.
The influence of two new 1-desoxynojirimycin derivatives, BAY m 1099 and BAY o 1248, on rat small intestinal disaccharidases (sucrase, maltase, isomaltase, glucoamylase, lactase, trehalase) and alkaline phosphatase activity has been investigated in vitro. Both compounds are very potent alpha-glucosidase inhibitors. Tested in the range of 0.1-5.0 micrograms/ml, inhibition is strongest on sucrase (up to 97.1%) and glucoamylase (up to 96.7%). BAY m 1099 also reduced (up to 56.4%) beta-galactosidase (lactase) activity. For both inhibitors a competitive type of sucrase inhibition was demonstrated (Lineweaver-Burk plot). Affinity versus sucrase was unusually tight. The Ki of BAY m 1099 versus sucrase amounted to 1.14 x 10(-7) M and of BAY o 1248 to 6.92 X 10(-8) M (Dixon plot). Both inhibitors did not impair active transport of L-leucine or methyl-alpha-D-glucoside into everted rings of rat jejunum in vitro.
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001693:Biological Transport, Active; D004186:Disaccharidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D050112:Imino Pyranoses; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D007421:Intestine, Small / Q000201:enzymology*; D007930:Leucine / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D050112:Imino Pyranoses; D008757:Methylglucosides; C045621:miglitol; D017485:1-Deoxynojirimycin; C027020:methylglucoside; D000469:Alkaline Phosphatase; D004186:Disaccharidases; D007930:Leucine; D005944:Glucosamine; C045622:emiglitate