Uptake of gamma-aminobutyric acid and glycine by synaptosomes from postmortem human brain.
Synaptosomes prepared from frozen postmortem human brain accumulated the neurotransmitter gamma-aminobutyric acid (GABA) and the conformationally restricted GABA analogue cis-3-aminocyclohexanecarboxylic acid (ACHC) by a sodium-dependent, temperature-sensitive, high-affinity transport process into an osmotically sensitive compartment. This transport process could be inhibited by GABA analogues (ACHC, 2,4-diaminobutyric acid, nipecotic acid, arecaidine, guvacine) that have been shown in studies on other species to be relatively selective for neuronal rather than glial uptake systems, whereas the glial uptake inhibitor beta-alanine was ineffective. Synaptosomes prepared from frozen post-mortem human medulla and spinal cord, but not cerebral cortex, took up the neurotransmitter glycine by a sodium-dependent high-affinity transport process. The kinetic parameters for the high-affinity uptake of GABA, ACHC, and glycine were Km = 10 +/- 3, 49 +/- 19, and 35 +/- 19 microM; and Vmax = 98 +/- 15, 84 +/- 25, and 5.5 +/- 2.5 nmol/min/100 mg protein, respectively. These results demonstrate the feasibility of using human CNS preparations for studying GABA and glycine uptake, and suggest that such studies may be useful neurochemical markers for transmitter-specific presynaptic terminals in health and disease.
D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D000598:Amino Acids, Cyclic; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008875:Middle Aged; D011180:Postmortem Changes; D012964:Sodium / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; C015666:3-aminocyclohexanecarboxylic acid; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D005998:Glycine