Role of receptor internalization in the agonist-induced desensitization of cannabinoid type 1 receptors.

摘要: Agonist-induced internalization of G protein-coupled receptors (GPCRs) is an important mechanism for regulating signaling transduction functional at the plasma membrane. We demonstrate here that both caveolae/lipid-rafts- and clathrin-coated-pits-mediated pathways were involved in agonist-induced endocytosis cannabinoid type 1 receptor (CB1R) stably transfected human embryonic kidney (HEK) 293 cells internalized predominantly sorted into recycling pathway reactivation. The treatment CB1 with low endocytotic agonist Δ9-THC induced a faster desensitization slower resensitization than high WIN 55,212-2. In addition, blockade or markedly enhanced desensitization. Furthermore, co-expression phospholipase D2, enhancer endocytosis, reduced desensitization, whereas D2 negative mutant significantly increased after 55,212-2 treatment. These findings provide evidences importance counteracting by facilitating Moreover, primary cultured neurons, anandamide exhibited greater endogenous 55,212-2, CP 55940 2-arachidonoyl glycerol, indicating cannabinoids efficacy might cause development tolerance to some kind cannabinoid-mediated effects.