Rj. Thurlow et al., [H-3] GABAPENTIN MAY LABEL A SYSTEM-L-LIKE NEUTRAL AMINO-ACID CARRIERIN BRAIN, European journal of pharmacology. Molecular pharmacology section, 247(3), 1993, pp. 341-345
The ability of large neutral amino acids to interact with a site in mo
use and pig brain labelled by [H-3]gabapentin was examined. As previou
sly described for rat tissue, [H-3]gabapentin bound to synaptic plasma
membranes prepared from mouse or pig cerebral cortex with high affini
ty (Kinetically derived K(D) = 14 and 17 nM for mouse and pig, respect
ively). Equilibrium binding in each species was inhibited by gabapenti
n and a range of large neutral amino acids. L-leucine (IC50 = 80 nM),
L-isoleucine (IC50 = 72 nM), L-norleucine (IC50 = 40 nM) and L-methion
ine (IC50 = 50 nM) were the most potent of those tested. Binding was a
lso inhibited by L-phenylalanine (IC50 = 380 nM), L-valine (IC50 = 310
nM) and the selective system-L substrate 2-amino-2-carboxy-bicyclohep
tane (IC50 = 420 nM) but not by the sodium-dependent System-A substrat
e methylaminoisobutyric acid. The presence of a submaximal concentrati
on of leucine reduced [H-3]gabapentin binding affinity but did not aff
ect the maximum number of binding sites, suggesting a competitive inte
raction between leucine and the binding protein. The results suggest [
H-3]gabapentin may label a site in brain that resembles the large neut
ral amino acid transporter described in other tissues.