RESUMO
The interaction between ethanol and cysteine sulfinic acid was examined in male Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measurement of central nervous system depression. In addition, the interaction between ethanol and cysteic acid, a metabolite of cysteine sulfinic acid, was studied. Immediately after the animals regained the righting reflex following ethanol injection (IP), mice were given an ICV injection of saline, cysteine sulfinic acid (1, 15 or 25 mumol/kg) or cysteic acid (1, 15, or 25 mumol/kg). There occurred a return to the LORR within 30 s after the ICV injection of drugs. The return to the LORR by the administration of the amino acids in the presence of ethanol occurred in a dose-dependent fashion. When cysteine sulfinic acid or cysteic acid (25 mumol/kg, ICV) was injected in the absence of ethanol, no loss of the righting reflex occurred. In other experiments, bicuculline methiodide was given ICV with cysteine sulfinic acid (25 mumol/kg), cysteic acid (25 mumol/kg), or GABA (25 mumol/kg) in the presence of ethanol. Bicuculline methiodide, a GABA antagonist, reduced the effects of the three amino acids to produce a return to the LORR in the presence of ethanol. These results indicate that cysteine sulfinic acid, an excitatory amino acid, and cysteic acid can enhance the central depressant properties of ethanol. Since bicuculline antagonized the effects of these two amino acids, a GABAergic mechanism may be involved in the interaction between ethanol and cysteine sulfinic acid or cysteic acid.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Cisteína/análogos & derivados , Etanol/farmacologia , Neurotransmissores/farmacologia , Animais , Bicuculina/análogos & derivados , Bicuculina/farmacologia , Ácido Cisteico/administração & dosagem , Ácido Cisteico/antagonistas & inibidores , Ácido Cisteico/farmacologia , Cisteína/administração & dosagem , Cisteína/antagonistas & inibidores , Cisteína/farmacologia , Sinergismo Farmacológico , Antagonistas GABAérgicos , Injeções Intraventriculares , Masculino , Camundongos , Equilíbrio Postural/efeitos dos fármacosRESUMO
The content of free amino acids in rat brain changes uniformly (serine, taurine, GABA, alanine, valine, cystine, leucin, phenylalanine) as a result of injecting rats with cyanide (60 mg/kg) or cyanide in conjunction with ethanol (0.5 g/kg). In addition, in the latter case the level of cysteic acid and ornithine decreases 2-fold.
Assuntos
Aminoácidos/metabolismo , Encéfalo/metabolismo , Cianamida/administração & dosagem , Cianetos/administração & dosagem , Acetaldeído/metabolismo , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído Desidrogenase/metabolismo , Animais , Ácido Cisteico/antagonistas & inibidores , Sinergismo Farmacológico , Etanol/administração & dosagem , Injeções Intraperitoneais , Masculino , Ornitina/antagonistas & inibidores , RatosRESUMO
DL-alpha-Aminoadipate (DLalphaAA) and L-glutamic acid diethylester (GDEE) were compared as antagonists of the excitatory effects of a number of amino acids on interneurones, and also of acetylcholine on Renshaw cells of the cat spinal cord. The excitants could be ranked in order of their sensitivity of the two antagonists. Ibotenate and the optical isomers of N-methylaspartate were the most readily antagonised by DLalphaAA and the least by GDEE; L-glutamate and quisqualate were most affected by GDEE and least by DLalphaAA; the actions of L-cysteate, L-aspartate and D- and L-homocysteate were reduced to some extent by both; and kainate was relatively insensitive to both antagonists. Acetylcholine excitations of Renshaw cells were often reduced by GDEE and occasionally by DLalphaAA. The results indicate the existence on spinal neurones of at least two populations of amino acid receptors which have differing sensitivities to the antagonists, and which do not precisely conform to the "glutamate-perferring" and "aspartate-preferring" categories which have been proposed on other grounds.