Hydrolysis of 1, 2 diacylglycerol lipase by DAG. The endocannabino By a plurality of cell types, Confinement Lich endothelial cells, adipocytes, glial cells, macrophages, and the Purkinje cells produces. In the brain, 2 AG is bioactive and abundant relative to the AEA. Both AEA and 2 male metabolized by the cell membrane by a hydrolase fat Ureamid NVP-BKM120 BKM120 transported, but can also cut two AG monoacylglycerol lipase, serine hydrolase. The first evidence for the existence of a cannabinoid receptor Of was obtained from pharmacological studies. Treatment of neuroblastoma cells with Δ 9-THC, or with the synthetic compounds and levonantradol desacetyllevonantradol, showed an inhibition of the activity T of the plasma membrane adenylate cyclase, the enzyme that catalyzes the conversion of ATP to 3, 5 cyclic AMP and pyrophosphate.
However, it has been shown that dextronantradol no effect on this activity PXD101 T compared to levonantradol indicating that the inhibition was stereoselective, a prerequisite for participation have a receptor-mediated actions. Other studies have shown that the cannabinoid receptor Coupled from Mutma Lichen an inhibitory guanine nucleotide-binding complex is, since the treatment with pertussis toxin reversed the inhibitory effect of adenylate cyclase. By using the radioligand binding assay and in situ hybridization of mRNA was demonstrated that the receptor was distributed in the brain and Haupt Normally in the cerebellum, Gro Cerebral cortex, hippocampus, the localized, basal ganglia and the spinal cord.
Subsequently End of the receptor was isolated and cloned from a library of rat brain cDNA encoding acids for a revealing 473 amino Long, seven-transmembrane G-protein-coupled protein. This receiver was originally designed as neural or central cannabinoid receptor Of known and has been called cannabinoid receptor First CB1 negatively regulates the release of neurotransmitters by inhibiting the phosphorylation of potassium channels Len of type A. It has been reported that the current potassium channel potassium may Str Me of type A non-phosphorylated to prevent neurotransmission. N-type calcium channels Le are also inhibited by CB1 through direct interaction with the inhibitory G protein. Restrict CB1 LIMITATION neurotransmission on potassium and calcium channels Le accounts for Cognitive and sedative effects of marijuana users experience as taught.
After the identification of CB1, a cannabinoid receptor was Ger cloned T or from a non-neuronal human promyelocytic cell cDNA library, and was as cannabinoid receptor Second The gene for this receptor has been shown that a 360 Amino acids Long encode seven-transmembrane G-protein-coupled receptors with comparable CB1 has been found that an extracellular Re glycosylated N-terminus and C-terminus have intracellular r. Unlike CB1, there is a considerable Ma of sequence variation for Cabral and Thomas Griffin Page 2 Expert Rev Mol Med Author manuscript, increases available in PMC 2010, the first January. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH CB2 between humans, M Mice and rat species, especially when comparing the sequences of rat and man. It has 81% amino Acid identity T between rat and human CB2, compared with an amino Acid identity t of 93% between rat and mouse CB2. It was reported that the rat CB2 sequence Sequenzidentit T points in the carboxy-terminus in comparison to various mouse and human CB2 sequences, and that the presence of the intron