Modulation of gamma-aminobutyric acid uptake of rat brain synaptosomes by thyroid hormones.
The effects of thyroid hormones on gamma-aminobutyric acid (GABA) uptake were compared in homogenates and purified synaptosomes from rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4), but not reverse T3(rT3), blocked GABA uptake in homogenates when hormone and labeled GABA were added to the system simultaneously. Similar effects were obtained when homogenates were preincubated with hormone and washed to remove free hormone before addition of GABA. A competitive inhibitor of neuronal GABA uptake, diaminobutyric acid (DABA), blocked GABA uptake when added with GABA, but not after preincubation and washing. In purified synaptosomes, T3, T4, and rT3 blocked GABA uptake when added simultaneously with GABA and also after preincubation and washing before addition of GABA, thus indicating that binding of hormones had occurred. Other experiments suggested that hormone binding was not at the GABA recognition site and that the effect of T4 was not dependent on conversion to T3.
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D005680:gamma-Aminobutyric Acid; D013974:Thyroxine