Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes.

阅读量:

78

作者:

AC HowlettRM Fleming

展开

摘要:

The inhibition of adenylate cyclase activity by cannabimimetic compounds in a membrane fraction from cultured neuroblastoma cells has been examined. The inhibition was shown to be concentration-dependent over a nanomolar range for both delta 9-tetrahydrocannabinol and its synthetic analog, desacetyllevonantradol. Inhibition was rapid and reversible. The cannabimimetic compounds caused a decrease in Vmax of the enzyme, with no alteration in the Km for substrate. The effects of these compounds were related to the ability of the enzyme to be regulated by divalent cations and guanine nucleotides. The inhibition was greatest at micromolar Mg2+ or Mn2+ concentrations and was abolished at less than 1 mM MnCl2. In the hormone-stimulated state, the enzyme appeared to be regulated by one Mg2+ site. The addition of cannabimimetic or muscarinic cholinergic agents transformed the enzyme into one in which more complex regulation by divalent cations was observed. Half-maximal inhibition of adenylate cyclase was observed at 800 nM GTP for both cannabimimetic and muscarinic cholinergic agents. The substitution for GTP of a nonhydrolyzable analog resulted in activation of the enzyme and failure to respond to either class of inhibitory agents. If the Mg2+ concentration was reduced and exposure to the GTP analog was of short duration, inhibition by both cannabimimetic and muscarinic agents could be observed in the presence of forskolin. This study points to the similarities between the enzyme inhibition by cannabimimetic compounds and by muscarinic cholinergic compounds. It is inferred that the cannabimimetic compounds must act via regulatory mechanisms similar to those operating for receptor-mediated inhibition of adenylate cyclase.

展开

DOI:

10.1002/med.2610040405

被引量:

839

年份:

1985

通过文献互助平台发起求助,成功后即可免费获取论文全文。

相似文献

参考文献

引证文献

来源期刊

引用走势

1998
被引量:48

辅助模式

0

引用

文献可以批量引用啦~
欢迎点我试用!

关于我们

百度学术集成海量学术资源,融合人工智能、深度学习、大数据分析等技术,为科研工作者提供全面快捷的学术服务。在这里我们保持学习的态度,不忘初心,砥砺前行。
了解更多>>

友情链接

百度云百度翻译

联系我们

合作与服务

期刊合作 图书馆合作 下载产品手册

©2025 Baidu 百度学术声明 使用百度前必读

引用