Baltrons M A, Agulló L, García A
Instituto de Biología Fundamental V. Villar Palasí, Universidad Autónoma de Barcelona, Bellaterra, Spain.
J Neurochem. 1995 Jan;64(1):447-50. doi: 10.1046/j.1471-4159.1995.64010447.x.
Treatment of rat cerebellar astrocyte-enriched primary cultures with dexamethasone enhances the nitric oxide-dependent cyclic GMP formation induced by noradrenaline in a time-(> 6 h) and concentration-dependent manner (half-maximal effect at 1 nM). Stimulation of cyclic GMP formation by the calcium ionophore A23187 is similarly enhanced. In contrast, cyclic GMP accumulation in cells treated with lipopolysaccharide is inhibited by dexamethasone. The potentiating effect of dexamethasone is prevented by the protein synthesis inhibitor cycloheximide and is not due to increased soluble guanylate cyclase activity. Agonist stimulation of [3H]arginine to [3H]citrulline conversion is enhanced by dexamethasone in astrocytes but not in cerebellar granule cells. These results indicate that glucocorticoids may up-regulate astroglial calcium-dependent nitric oxide synthase while preventing expression of inducible nitric oxide synthase and are the first report of a differential long-term regulation of the expression of neuronal and astroglial constitutive nitric oxide synthase activities.
用地塞米松处理富含大鼠小脑星形胶质细胞的原代培养物,能以时间(> 6小时)和浓度依赖的方式(1 nM时达到半数最大效应)增强去甲肾上腺素诱导的一氧化氮依赖性环磷酸鸟苷(cGMP)生成。钙离子载体A23187对cGMP生成的刺激作用也同样增强。相比之下,地塞米松可抑制脂多糖处理细胞中的cGMP积累。地塞米松的增强作用可被蛋白质合成抑制剂环己酰亚胺阻断,且并非由于可溶性鸟苷酸环化酶活性增加。地塞米松可增强星形胶质细胞中激动剂刺激的[3H]精氨酸向[3H]瓜氨酸的转化,但对小脑颗粒细胞无此作用。这些结果表明,糖皮质激素可能上调星形胶质细胞钙依赖性一氧化氮合酶,同时抑制诱导型一氧化氮合酶的表达,这是关于神经元和星形胶质细胞组成型一氧化氮合酶活性表达的差异性长期调节的首次报道。