Intracellular cannabinoid type 1 (CB1) receptors are activated by anandamide. Academic Article uri icon

start page

  • 29166

end page

  • 29174

abstract

  • Recent studies have demonstrated that the majority of endogenous cannabinoid type 1 (CB(1)) receptors do not reach the cell surface but are instead associated with endosomal and lysosomal compartments. Using calcium imaging and intracellular microinjection in CB(1) receptor-transfected HEK293 cells and NG108-15 neuroblastoma × glioma cells, we provide evidence that anandamide acting on CB(1) 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 CB(1) 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 CB(1) receptor-transfected HEK293 cells, intracellular CB(1) receptors are functional; they are located in acid-filled calcium stores (endolysosomes). Activation of intracellular CB(1) 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.

date/time value

  • 2011

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.217463

PubMed Identifier

  • 21719698

volume

  • 286

number

  • 33

keywords

  • Arachidonic Acids
  • Calcium
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Endocannabinoids
  • Endosomes
  • HEK293 Cells
  • Humans
  • Lysosomes
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1