Neuronal and glial plasma membrane carrier-mediated uptake of L-homocysteate is not selectively blocked by beta-p-chlorophenylglutamate.
The proposed action of beta-p-chlorophenylglutamate (chlorpheg) as a selective blocker of L-homocysteate uptake was studied in primary cultures of mouse brain neurons and astrocytes and in rat brain synaptosomes. The preparations were incubated with 1 microM to 10 mM L-homocysteate and D-aspartate in the absence and presence of 7.5 mM chlorpheg. In each preparation uptake of the two amino acids comprised a saturable uptake and a non-saturable (passive diffusion) component. L-Homocysteate was of at least 100-fold lower affinity than D-aspartate as a substrate for the amino acid transporter. Chlorpheg was shown to be essentially equieffective as a weak competitive inhibitor of only the saturable uptake of L-homocysteate and D-aspartate. It is concluded that chlorpheg is not a selective blocker of L-homocysteate uptake.
Griffiths
R
R
Division of Biochemistry and Molecular Biological and Medical Sciences, University of St. Andrews, Fife, UK.
Grieve
A
A
Allen
S
S
Olverman
H J
HJ
D026905:Amino Acid Transport Systems; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D005971:Glutamates; D006710:Homocysteine; C007956:homocysteic acid; C045418:3-(4-chlorophenyl)glutamic acid