Gonzales J M, Méndez-Bobé I
Department of Anesthesiology, Medical College of Pennsylvania, Philadelphia 19102-1192, USA.
Anesthesiology. 1996 May;84(5):1148-55. doi: 10.1097/00000542-199605000-00017.
Cyclic adenosine monophosphate (cAMP) is an important regulator of neuronal excitability. The effects of barbiturates on cAMP production in intact neurons are not known. This study used cultures of cortical neurons, cultures of glia, and slices of cerebral cortex from the rat to study the effects of barbiturates on cAMP regulation in the brain.
Primary cultures of cortical neurons or glia were prepared from 17-day gestational Sprague-Dawley rat fetuses and were used after 12-16 days in culture. Cross-cut slices (300 microns) were prepared from cerebral cortex of adult rats. Cyclic AMP accumulation was determined by measuring the conversion of [3H]adenosine triphosphate (ATP) to [3H]cAMP in cells preloaded with [3H]adenine.
Pentobarbital enhanced isoproterenol- and forskolin-stimulated, but not basal, cAMP accumulation in cultures of cerebral neurons. Cyclic AMP production was enhanced by pentobarbital in a dose-dependent fashion up to a concentration of 250 microM; This concentration of pentobarbital increased cAMP production by 40-50% relative to that in controls without pentobarbital. At 500 microM pentobarbital, the magnitude of the enhancement was less. Pentobarbital had no effect on isoproterenol-stimulated cAMP production in cultures containing only glia. Pentobarbital also enhanced isoproterenol-stimulated, but not basal, cAMP production in slices of cerebral cortex by approximately 30% at concentrations of 62.5-250 microM and by almost 100% at 500 microM.
Pentobarbital enhances stimulated cAMP accumulation in cultured preparations from brain and fresh cortical slices. Neurons are required for this effect. Because cAMP modulates neuronal excitability, this effect of pentobarbital may be an important mechanism by which this anesthetic influences brain function.
环磷酸腺苷（cAMP）是神经元兴奋性的重要调节因子。巴比妥类药物对完整神经元中cAMP生成的影响尚不清楚。本研究利用大鼠的皮质神经元培养物、神经胶质培养物和大脑皮质切片来研究巴比妥类药物对大脑中cAMP调节的影响。
从妊娠17天的斯普拉格-道利大鼠胎儿制备皮质神经元或神经胶质的原代培养物，并在培养12 - 16天后使用。从成年大鼠的大脑皮质制备横切切片（300微米）。通过测量预先加载[³H]腺嘌呤的细胞中[³H]三磷酸腺苷（ATP）向[³H]cAMP的转化来测定cAMP的积累。
戊巴比妥增强了异丙肾上腺素和福斯高林刺激的大脑神经元培养物中cAMP的积累，但对基础cAMP积累无增强作用。戊巴比妥以剂量依赖的方式增强cAMP生成，直至浓度达到250微摩尔/升；该浓度的戊巴比妥使cAMP生成相对于无戊巴比妥的对照组增加40 - 50%。在500微摩尔/升戊巴比妥时，增强幅度较小。戊巴比妥对仅含神经胶质的培养物中异丙肾上腺素刺激的cAMP生成无影响。戊巴比妥还增强了大脑皮质切片中异丙肾上腺素刺激的cAMP生成，但对基础cAMP生成无增强作用，在浓度为62.5 - 250微摩尔/升时增加约30%，在500微摩尔/升时增加近100%。
戊巴比妥增强了来自大脑的培养制剂和新鲜皮质切片中刺激的cAMP积累。这种作用需要神经元。由于cAMP调节神经元兴奋性，戊巴比妥的这种作用可能是该麻醉药影响脑功能的重要机制。
