期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 33, 页码 29166-29174出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.217463
关键词
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资金
- National Institutes of Health [HL90804, DA023204, DA05274]
- Sunset Molecular Discovery (Santa Fe, NM)
Recent studies have demonstrated that the majority of endogenous cannabinoid type 1 (CB1) receptors do not reach the cell surface but are instead associated with endosomal and lysosomal compartments. Using calcium imaging and intracellular microinjection in CB1 receptor-transfected HEK293 cells and NG108-15 neuroblastoma x glioma cells, we provide evidence that anandamide acting on CB1 receptors increases intracellular calcium concentration when administered intracellularly but not extracellularly. The calcium-mobilizing effect of intracellular anandamide was dose-dependent and abolished by pretreatment with SR141716A, a CB1 receptor antagonist. The anandamide-induced calcium increase was reduced by blocking nicotinic acid-adenine dinucleotide phosphate-or inositol 1,4,5-trisphosphate-dependent calcium release and abolished when both lysosomal and endoplasmic reticulum calcium release pathways were blocked. Taken together, our results indicate that, in CB1 receptor-transfected HEK293 cells, intracellular CB1 receptors are functional; they are located in acid-filled calcium stores (endolysosomes). Activation of intracellular CB1 receptors releases calcium from endoplasmic reticulum and lysosomal calcium stores. In addition, our results support a novel role for nicotinic acid-adenine dinucleotide phosphate in cannabinoid-induced calcium signaling.
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