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.