Glutamate uptake into synaptic vesicles--inhibition by sulphur amino acids.
In an attempt to investigate the apparent absolute selectivity of the synaptic vesicle L-glutamate carrier, L- and D-enantiomers of excitatory sulphur-containing amino acid (SAA) transmitter candidates (which are close structural analogues of L-glutamate) were tested for their capacity to compete for vesicular L-[3H]-glutamate uptake. All SAAs inhibited, to varying degrees (52-86%), the vesicular uptake of L-[3H]-glutamate. A similar level of inhibition was exerted by SAAs with either a shorter or equal carbon chain length to L-glutamate. Moreover, inhibition was stereospecific in favour of the D-enantiomers. These studies indicate an appreciable interaction of the SAAs with the recognition site of the vesicular L-glutamate carrier. Further investigations are required to establish the substrate potential of the SAAs.
Department of Biochemistry and Microbiology, University of St. Andrews, Fife, Scotland, UK.
J
J
Dunlop
A
A
Fear
R
R
Griffiths
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D005971:Glutamates; D018377:Neurotransmitter Agents; D006710:Homocysteine; D018698:Glutamic Acid; D003545:Cysteine