Abstract
6-Aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide hydrochloride (TAG) applied by microiontophoresis caused a prompt and readily reversible antagonism of the inhibitory effects of taurine and beta-alanine on rat somatosensory cerebral cortical neurons and cerebellar Purkinje neurons, although not affecting the actions of gamma-aminobutyric acid. TAG also consistently reduced, but did not abolish, the synaptically evoked inhibitions of Purkinje cells produced by electrical stimulation of the cerebellar surface. On the isolated amphibian spinal cord, TAG caused a dose-related enhancement of the dorsal root-ventral root potential, although not substantially affecting the dorsal root-dorsal root potential. Qualitative studies on the amphibian spinal cord showed that the depolarizing actions of taurine and beta-alanine on the dorsal roots, but not those of gamma-aminobutyric acid or glycine, were reduced by TAG. Somewhat surprisingly, TAG also offset the inhibitory effects on cortical cells and the dorsal root depolarizing actions of muscimol, 3-aminopropane sulfonic acid and piperidine-4-sulfonic acid, all of which heretofore have been considered as selective gamma-aminobutyric acid agonists. These findings would appear to lend a substantial degree of credence to the repeated suggestions that taurine may subserve a neurotransmitter-type function in the mammalian central nervous system. Furthermore, the availability of a relatively specific antagonist might reasonable be expected to facilitate efforts to elucidate the physiological functions of taurine not only in the central nervous system but in other organ systems in the body as well.
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