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Synaptosomal plasma membrane transport of excitatory sulphur amino acid transmitter candidates: Kinetic characterisation and analysis of carrier specificity

✍ Scribed by A. Grieve; S. P. Butcher; Dr. Roger Griffiths


Book ID
102912970
Publisher
John Wiley and Sons
Year
1992
Tongue
English
Weight
886 KB
Volume
32
Category
Article
ISSN
0360-4012

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✦ Synopsis


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, = 57 f 6 pM; V,,, = 1.2 .t 0.1 nmoll min/mg protein) and L-CA (K, = 23 2 3 pM; V,,, = 3.6 +-0.1 nmol/min/mg protein), whereas L-HCSA (K, = 502 2 152 pM; V,,, = 6.1 k 1.3 nmoll minlmg protein) and L-HCA (K, = 1550 2 169 pM; V,,, = 10.3 +-1.1 nmollminlmg 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-[3H]glutamate, L-PHIaspartate, or D-[3H]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 [3H] y-aminobutyric acid (GABA) and [3H]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.