Regulation of calcium by delta9-tetrahydrocannabinol

δ9-四氢大麻酚对钙的调节

• 批准号: 6931980
• 负责人: GAUTHAM K RAO
• 金额: $ 1.01万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-16 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931980
• 关键词: T lymphocyte; autoradiography; calcium; calcium flux; calmodulin dependent protein kinase; cannabinoids; enzyme linked immunosorbent assay; gel mobility shift assay; interleukin 2; laboratory mouse; lymphocyte proliferation; predoctoral investigator; protein kinase C; receptor expression

DESCRIPTION (provided by applicant): Previous studies from this and other laboratories have demonstrated that delta9-tetrahydrocannabinol (delta9-THC), the primary psychoactive constituent in marijuana, can inhibit the expression of interleukin (IL)-2 by activated T cells. However, it remains unclear what role the cannabinoid receptors play in the regulation of IL-2 production by cannabinoids. Here, experiments were performed in murine splenic T cells or human T cell lines, HPB-ALL and Jurkat E6-1. The splenic T cells express both CB1 and CB2 receptor transcripts whereas the human T cells only express CB2 transcripts. Moreover, while HPB-ALL cells express normal CB2 receptors, the Jurkat E6-1 cells express dysfunctional CB2 receptors. Preliminary data using these cell models suggest that delta9-THC may inhibit IL-2 production via a premature rise in intracellular calcium ([Ca2+]i) in a cannabinoid receptor dependent manner. This research will be further pursued with the hypothesis that the inhibition of interleukin-2 expression by delta9-THC involves cannabinoid receptor-dependent elevation of [Ca((]i activation of calcium-dependent enzymes, protein kinase C (PKC) and calcium-dependent calmodulin kinase II (CaMKII), and modulation of nuclear factor of activated T cells (NFAT) activation. Future studies will be performed in the splenic T cells or HPB-ALL cells with three specific aims (SA). SA1) Investigation of the mechanism of [Ca2+]i elevation by ((-THC. SA2) Characterization of the effect of delta9-THC on PKC and CaMKII activation. SA3) Examination of the effect of delta9-THC-mediated elevation in [Ca2+]i on NFAT activation and IL-2 expression.

描述（由申请人提供）：