INTESTINAL-ABSORPTION OF ALPHA-METHYLDOPA - INVITRO MECHANISTIC STUDIES IN RAT SMALL INTESTINAL SEGMENTS

  • 1 August 1987
    • journal article
    • research article
    • Vol. 242  (2) , 443-449
Abstract
The mechanism of intestinal uptake of .alpha.-methyldopa (Aldomet) was investigated using isolated segments of rat small intestine. Incubations were limited to 2 to 5 min as histological examination of the tissue showed significant loss of structural integrity after 10 to 20 min at 37.degree. C. .alpha.-Methyldopa in the tissue was extracted and assayed by high-pressure liquid chromatography. Corrections were applied for uptake into extracellular spaces using inulin (14C). Uptake was temperature- and concentration-dependent (Km .simeq. 10 mM), was dependent on the location in the small intestine and was inhibited by ouabain (2 mM) or lack of sodium or glucose in the incubation medium. .alpha.-Methyldopa uptake also was inhibited by other neutral amino acids. The mucosal cell layer accounted for approximately 50% of the total drug accumulated in the tissue. Uptake was less when the serosal surface was exposed than when the tissue was everted. The similarity in uptake parameters between .alpha.-methyldopa and L-phenylalanine (parallel experiments) suggests that .alpha.-methyldopa is principally absorbed into rat small intestinal mucosal cells via an amino acid transport system.