Studies on the Metabolism of D- and L-Isomers of 3, 4-Dihydroxyphenylalanine (DOPA). V. Mechanism of Intestinal Absorption of D- and L-DOPA-¹⁴C in Rats

Abstract

The rate and mechanism of intestinal absorption of D- and L-isomers of 3, 4-dihydroxyphenylalanine (DOPA) were comparatively investigated in rats by means of in situ ligated loop and in vitro tissue accumulation techniques. L-DOPA was found to be very easily and much more rapidly absorbed from the ligated loop of rat intestine than the D-isomer and the absorption was proved to follow saturation kinetics and to be inhibited competitively by L-alanine and L-phenylalanine, while not by D-phenylalanine and D-DOPA. The in vitro tissue uptake of L-DOPA-¹⁴C revealed an accumulation of radioactivity against the concentration gradient, which was depressed by metabolic inhibitors as DNP and sodium azide. L-DOPA was extensively metabolized in the intestinal tissue to dopamine, its glucuronide and DOPAC, while the D-isomer was not metabolized to any appreciable extent. The rate of absorption and the tissue uptake of L-DOPA-¹⁴C was, however, not affected by inhibition of DOPA-decarboxylase. A saturability of the intestinal DOPA-decarboxylase activity with the substrate was demonstrated by everted sac method with increasing L-DOPA concentration in the incubation medium. From these results, it was concluded that L-DOPA, but not D-DOPA, is absorbed from rat intestine by an active transport mechanism, which proceeds independently from the decarboxylation process. These differences between the two isomers were also discussed in relation to those in their distribution patterns after oral administration to rats.