title: Substrate-specific regulation of the taurine transporter in human placental choriocarcinoma cells (JAR).
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Jayanthi
authors.forename: S
authors.initials: S
authors.lastname: Ramamoorthy
authors.forename: V B
authors.initials: VB
authors.lastname: Mahesh
authors.forename: F H
authors.initials: FH
authors.lastname: Leibach
authors.forename: V
authors.initials: V
authors.lastname: Ganapathy
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D002822:Choriocarcinoma / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D010920:Placenta / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism*; D015091:beta-Alanine / Q000494:pharmacology; D000099247:Taurine Transporters
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D003513:Cycloheximide; D003609:Dactinomycin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D012701:Serotonin; D012964:Sodium; D013654:Taurine; D015091:beta-Alanine; D000099247:Taurine Transporters; C003949:hypotaurine