- 作者: S. Yu; I.K. Ho
- 作者服務機構: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Miss., USA
- 中文摘要: --
- 英文摘要: The in vitro receptor-stimulated synaptoneurosomal chloride uptake induced by pentobarbital or muscimol was studied in the brains of rats which had been rendered tolerant to or dependent on pentobarbital. In the chronic study, rats received continuous administration of sodium pentobarbital by intracerebroventricular (i.c.v.) infusion. In rats continuously infused with pentobarbital for 6 days or in rats which had the infusion terminated for 24 h, the basal synaptoneurosomal chloride uptake was not altered in either the cerebral cortex or the cerebellum. On the other hand, pentobarbital (500 μA)-stimulated chloride uptake was significantly decreased in both cerebral cortices and cere-bella of rats which received pentobarbital for 6 days as compared with the saline control groups. Twenty-four hours after termination of pentobarbital infusion, this high concentration of pentobarbital-stimulated chloride uptake remained low in both cerebral cortices and cerebella of rats which had been infused with pentobarbital for 6 days. In addition, similar results were also obtained in muscimol (2.5 μM)-stimulated chloride uptake in the cerebral cortices of pentobarbital-infused animals. However, pentobarbital infusion failed to alter muscimol-stimulated chloride uptake in the cerebellum. These results suggest that the GABAa receptor regulated chloride uptake is downregulated after chronic pentobarbital administration. The results also suggest that down-regulation of the GABAA receptor chloride channel complex takes place at different recognition sites on the complex. It further substantiates the alloste-ric effects of GABA and barbiturate recognition sites.
- 中文關鍵字: --
- 英文關鍵字: Pentobarbital ; GAGAA receptor ; Chloride flux ; Synaptoneurosomes