Tsai San-Fu, Yang Chi, Wang Shun-Cheng, Wang Jiunn-Shiow, Hwang Jenn-Sheng, Ho Shu-Peng
Laboratory of Toxicology and Pharmacology, Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC.
Toxicol Appl Pharmacol. 2004 Jan 1;194(1):34-40. doi: 10.1016/j.taap.2003.08.015.
The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or 54-377% by thuringiensin at concentrations of 10 microM-100 mM or 0.5-4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1-100 microM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 microM)-stimulated adenylate cyclase activity at concentrations of 10 microM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase.
本研究旨在评估苏云金素对大鼠大脑皮层腺苷酸环化酶活性的影响。结果显示,在浓度为10微摩尔/升至100毫摩尔/升或0.5至4毫摩尔/升时,苏云金素可使环磷酸腺苷(cAMP)水平呈剂量依赖性升高17%至450%或54%至377%,这是由于大鼠大脑皮层膜制剂的基础腺苷酸环化酶活性被激活所致。苏云金素还可激活来自大肠杆菌的市售腺苷酸环化酶的基础活性。然而,在浓度为1至100微摩尔/升时,苏云金素会抑制大鼠大脑皮层中福斯高林刺激的腺苷酸环化酶活性,从而使cAMP生成减少。此外,在浓度为10微摩尔/升时,苏云金素或腺苷酸环化酶抑制剂(MDL - 12330A)可分别使福斯高林(10微摩尔/升)刺激的腺苷酸环化酶活性降低49%或43%。总之,本研究表明,苏云金素可激活大鼠大脑皮层或市售腺苷酸环化酶的基础腺苷酸环化酶活性,并增加cAMP浓度。比较苏云金素对基础和福斯高林刺激的腺苷酸环化酶活性的剂量依赖性影响,苏云金素可被视为腺苷酸环化酶的弱激活剂或福斯高林刺激的腺苷酸环化酶的抑制剂。