Exposure of the JAR human placental
choriocarcinoma cells to
taurine leads to a marked decrease in the activity of the
taurine transporter in these cells. The ability to induce this adaptive response is not unique to
taurine but is shared by other substrates of the transporter as well. Compounds such as
betaine and
alpha-aminoisobutyric acid which are not substrates for the transporter do not produce this effect. The change in the
taurine transporter activity induced by
taurine exposure is however unique to the
taurine transporter because the activities of many other transport systems remain unaffected under these conditions. The adaptive regulation is not associated with any change in the dependence of the transporter activity on Na+ and Cl-, in the Na+/Cl-/
taurine stoichiometry and in the affinities of the transporter for Na+ and Cl-. The decrease in the transporter activity caused by
taurine exposure is due to a decrease in the maximal velocity of the transporter, and to a lesser extent, in the substrate affinity of the transporter. The decrease in the transporter activity observed in intact cells is demonstrable in plasma membrane vesicles after isolation from control and
taurine-exposed cells.
Cycloheximide and
actinomycin D block the adaptive response in intact cells to a significant extent, but not completely. Northern blot analysis of
mRNA from control and
taurine-exposed cells shows that
taurine exposure causes a significant decrease in the steady state levels of the
taurine transporter mRNA. It is concluded that the activity of the
taurine transporter in JAR cells is subject to substrate-specific adaptive regulation and that transcriptional as well as posttranscriptional events are involved in this regulatory process.