CHARACTERISTICS OF THE TRANSPORT OF PTEROYLGLUTAMATE AND AMETHOPTERIN IN RAT JEJUNUM

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 216  (2) , 329-333
Abstract
Intestinal transport of pteroylglutamate and amethopterin, a folate antagonist, was characterized in everted sacs of rat jejunum. The system is composed of 2 distinguishable processes: active pH-dependent, carrier-mediated transport and diffusion. The active process is specific for the pteroylglutamate molecule and requires Na. When active transport is blocked completely by cyanide, iodoacetate, p-chloromercuriphenylsulfonate, the absence of Na or high concentrations (50-100 .mu.M) of the substrate, 20-30% 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 .simeq. 112 .mu.M) and amethopterin (Ki .simeq. 70 .mu.M) 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% and 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 .mu.g) in vitro. The mechanisms of intestinal folate transport are clarified and drug interactions which influence the transport process are described.