Amino acid inhibition of sodium-dependent synaptosomal proline uptake.

The inhibitory effects of several amino acids on the synaptosomal uptake of l-proline were studied. Phenylalanine, valine, isoleucine and histidine were most inhibitory (I(50) approximately 100 muM) while leucine, serine and tyrosine had lesser inhibitory effects. The inhibition by phenylalanine and valine was of the competitive type. The inhibitory effects were stereospecific since d-isomers of the amino acids had no effect on synaptosomal proline uptake. The uptakes of three other putative neurotransmitter amino acids, viz. aspartic acid, glutamic acid and gamma-aminobutyric acid, were not similarly affected by the amino acids and the inhibitory effects thus appear to be unique to proline uptake. These results raise the possibility that the uptake of proline at the nerve endings may be regulated by the amino acids.