| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 99 === Abstract
Endocannabinoid system involves in variety of physiological processes in our body such as appetite, mood and memory. Cannabinoid receptors contain two subtypes, i.e. cannabinoid receptor type 1 (CB1R) and type 2 (CB2R). Brain-enriched CB1R is a Gi/o-coupled receptor, when activated it can inhibit adenylyl cyclase activity and negatively regulate calcium channels. Previously in our laboratory, we found the expression of rat CB1R mRNA was down-regulated after chronic methamphetamine treatment. In addition, the dopamine (DA) D2R or CB1R activation could individually enhance ERK1/2 signal and produce synergistic effect when D2R and CB1 agonists were co-administered in the primary striatal cultures. These findings suggest a plausible D2R and CB1R cross-talk, at either cellular or nuclear level, in the striatum, however the details of cellular mechanism remains unclear. To answer these questions, I first adopted C6 glioma which carries endogenous CB1R and stably transfected with D2SR then treated with D2R and CB1R agonists and/or antagonists, individually or in combination, to explore the possible signal cross-talk. The results show that D2R antagonist could not effectively block CB1R-induced pERK1/2 signal, on the other hand CB1R could not also affect D2SR-induced ERK signal indicating that endogenous D2R/CB1R cross-talk might mediate through D2L receptor. Furthermore, to assess if D2R could regulate CB1R at transcription level, we constructed -0.2k and -0.4k promoter regions of the CB1R gene that exhibit differential luciferase activity under basal condition. I found that activation of D2R could enhance the expression of CB1R mRNA as well as promoter activity at specific upstream region(s). Based on these results, I hypothesize that DA pre-synaptic D2SR could modulate endocannabinoid system via regulation on CB1R expression in the striatum.
|
|---|
