The effect of trimethyltin on three glutamergic and gabaergic transmitter parameters in vitro: high affinity uptake, release and receptor binding.
The effects of trimethyltin (TMT) on high-affinity uptake, release and sodium-independent binding of glutamic acid and gamma-aminobutyric acid (GABA) were studied in vitro in homogenates of hippocampal tissue. TMT (50 micron) increased the release of glutamic acid from synaptosomes in the resting state (5 mM K+), whereas the release of GABA was only slightly affected. High affinity uptake of glutamate was inhibited by TMT in the same concentration range as release. The uptake of GABA was only affected by TMT-concentrations from 500 micron to 5 mM. The sodium independent binding of both glutamate and GABA, usually assumed to be binding to receptor sites, were inhibited with 50 microM or more TMT in the incubation medium. The results indicate that TMT can interfere with several different events of the neurotransmission process in the central nervous system at concentrations which can be obtained in the brain of rats after a sublethal dose of the compound.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium