Studies on uptake of gamma-aminobutyric acid by mouse brain particles; toward the development of a model.
Several substances were studied for their effect on enhancement and/or inhibition of uptake of GABA into a mouse brain microsomal fraction (P3) at pH 7.3 in the presence and absence of buffer. These were diverse: Na+, K+, NH4+, Hg2+, Cl-, and HCO3-; beta-guanidinopropionic and L-2,3-diaminopropionic acids and 1,2-diaminoethane; pyridine and several methylated pyridines; chlorpromazine and ketamine; and melittin. Kinetic experiments tested these substances for competition with GABA and Na+. Assuming the GABA transporter to consist of a GABA recognition entity and a Na+- and Cl-dependent protein required for its activity, a minimal provisional model for the GABA uptake process is proposed that is consistent with all current data and with relevant observations in the literature. It accounts for the activational effects of proton removal on GABA uptake, the stoichiometry of 2 Na+ and 1 Cl- associated with uptake of one GABA molecule, and the types of inhibition of uptake shown by the substances listed above. Factors are considered that may be necessary to maintain the transporter in a GABA-receptive configuration and that allow it the freedom of movement to undergo the structural variations necessary for the transport process to take place at rates that may be regulated by environmental factors.
Liron
Z
Z
Department of Neurobiochemistry, Beckman Research Institute, City of Hope, Duarte, CA 91010.
Wong
E
E
Roberts
E
E
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008959:Models, Neurological; D012964:Sodium / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D005680:gamma-Aminobutyric Acid; D012964:Sodium