Inhibition of sodium-dependent L-leucine uptake in rat brain synaptosomes.
Synaptosomes isolated from adult rat cerebral cortices were used for studying the uptake of L-leucine by the Na(+)-dependent route. Three non-metabolizable amino acid analogues, which had been used previously to discriminate the Na(+)-dependent A-type uptake system of animal cells, were employed in this study. It was found that Na(+)-dependent uptake of leucine was insensitive to inhibition by 2-aminoisobutyric acid (AIB) and N-methylaminoisobutyric acid (MeAIB) whereas N-methylalanine (NMA) was markedly inhibitory. Inhibition by NMA was stereospecific--only the L-isomer had a pronounced effect. Na(+)-dependent uptake of leucine as well as its inhibition by L-NMA were rather insensitive to changes in pH from 6 to 9. Kinetic analysis of inhibition by L-NMA of Na(+)-dependent uptake revealed a non-competitive type of inhibition with a Ki value of approximately 0.5 mM.
Tan
C H
CH
Department of Biochemistry, Faculty of Medicine, National University of Singapore.
Ng
F H
FH
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000621:Aminoisobutyric Acids; D002250:Carbon Radioisotopes; C100049:2-aminoisobutyric acid; C017911:2-(methylamino)isobutyric acid; C008408:N-methylalanine; D012964:Sodium; D007930:Leucine; D000409:Alanine