Characteristics of the transport of pteroylglutamate and amethopterin in rat jejunum.
Intestinal transport of pteroylglutamate and amethopterin, a folate antagonist, was further characterized in everted sacs of rat jejunum. The system is composed of two distinguishable processes: active, pH-dependent, carrier-mediated transport and diffusion. The active process is specific for the pteroylglutamate molecule and requires sodium. When active transport is blocked completely by cyanide, iodoacetate, p-chloromercuriphenylsulfonate, the absence of sodium or high concentrations (50-100 microM) of the substrate, 20 to 30% of the total substrate available is transported by diffusion. In contrast to the active process, the diffusion component is not pH-dependent. Sulfasalazine inhibits pteroylglutamate (Ki congruent to 112 microM and amethopterin K congruent to 70 microM) transport competitively and reduces the quantity of pteroylglutamate converted to 5-methyltetrahydrofolate during intestinal transport. Studies using identical concentrations of amethopterin covalently bound to albumin and free drug indicate that the covalently bound amethopterin is transported 18% as well as free drug by jejunal and ileal sacs. Ethanol (3g/dl) has a mild inhibitory effect on pteroylglutamate and amethopterin transport. Cholestyramine (20 mg) adsorbs 95% of pteroylglutamate or amethopterin (100 micrograms) in vitro. These studies further clarify the mechanisms of intestinal folate transport and describe drug interactions which influence the transport process.
D000818:Animals; D002792:Cholestyramine Resin / Q000494:pharmacology; D004058:Diffusion; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005492:Folic Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000378:metabolism*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology
D002792:Cholestyramine Resin; D012710:Serum Albumin, Bovine; D000431:Ethanol; D012460:Sulfasalazine; D005492:Folic Acid; D012964:Sodium; D008727:Methotrexate