Inhibition of synaptosomal uptake of amino acid transmitters by diamines.
Reports of the inhibitory effects of diaminocarboxylic acids on the uptake of amino acid transmitters led the present authors to examine the effects of simple aliphatic diamines on the synaptosomal uptake of glutamate, aspartate, GABA and glycine. The diamines studied were the series from ethylenediamine through to 1,7-diaminoheptane; DL-2,4-diaminobutyric acid (DABA) was also tested for comparative purposes. The greatest inhibition seen was on the uptake of glycine and GABA. Weaker effects on uptake were seen with glutamate, while aspartate was unaffected. The patterns of inhibition for glycine and GABA were similar and the effects were dose-dependent. 1,2-Diaminopropane was the most inhibitory, followed by ethylenediamine and 1,7-diaminoheptane. The reported inhibitory effects of DL-2,4-diaminobutyric acid on the uptake of GABA and glutamate were confirmed; comparable inhibition of the uptake of glycine and aspartate was seen but the effects on GABA were most potent. Inhibition of the uptake of GABA by 1,2-diaminopropane was approximately one fifteenth that reported for DL-2,4-diaminobutyric acid. The inhibition by diamine of the uptake of glycine and GABA can provide an explanation of the depressant effects of diamines, seen after ventricular administration; however, the excitotoxic effects of the diamines 1,3-diaminopropane through to 1,7-diaminoheptane could not be explained by the present results.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D003864:Depression, Chemical; D003959:Diamines / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D003959:Diamines; D005971:Glutamates; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine