SYNAPTOSOMAL PLASMA-MEMBRANE TRANSPORT OF EXCITATORY SULFUR AMINO-ACID TRANSMITTER CANDIDATES - KINETIC CHARACTERIZATION AND ANALYSIS OF CARRIER SPECIFICITY

The transport kinetics of the excitatory sulphur-containing amino acid (SAA) transmitter candidates, L-cysteine sulphinate (L-CSA), L-cysteate (L-CA), L-homocysteine sulphinate (L-HCSA), and L-homocysteate (L-HCA), together with their plasma membrane carrier specificity, was studied in cerebrocortical synaptosome fractions by a sensitive high performance liquid chromatographic assay. A high affinity uptake system could be demonstrated for L-CSA (K(m) = 57 +/- 6-mu-M; V(max) = 1.2 +/- 0.1 nmol/min/mg protein) and L-CA (K(m) = 23 +/- 3-mu-M; V(max) = 3.6 +/- 0.1 nmol/min/mg protein), whereas L-HCSA (K(m) = 502 +/- 152-mu-M; V(max) = 6.1 +/- 1.3 nmol/min/mg protein) and L-HCA (K(m) = 1550 +/- 169-mu-M; V(max) = 10.3 +/- 1.1 nmol/min/mg protein) exhibited much lower affinity as transport substrates. In all cases, only a single, saturable Na+-dependent component of uptake could be identified, co-existing with a non-saturable, Na+-independent influx component. Plasma membrane carrier specificity of the SAAs was established following comparison with other high-affinity neurotransmitter systems. High-affinity L-CSA and L-CA transport and low-affinity L-HCSA and L-HCA transport demonstrate strong positive correlations in inhibition profiles when compared against each other or individually against the high-affinity transport of L-[H-3]glutamate, L-[H-3]aspartate, or D-[H-3]aspartate. Moreover, the transport systems for the excitatory SAAs exhibited a negative correlation when compared in inhibition profiles with the high affinity transport of both [H-3] gamma-aminobutyric acid (GABA) and [H-3]taurine. Taken together, these results strongly suggest that L-CSA, L-CA, L-HCSA, and L-HCA share a common synaptosomal plasma membrane transport system with L-glutamate, L-aspartate, and D-aspartate.