Background
This gene encodes one of two cannabinoid receptors. The cannabinoids, principally delta-9-tetrahydrocannabinol and synthetic analogs, are psychoactive ingredients of marijuana. The cannabinoid receptors are members of the guanine-nucleotide-binding protein (G-protein) coupled receptor family, which inhibit adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. The two receptors have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. Multiple transcript variants encoding two different protein isoforms have been described for this gene.
Function
G protein-coupled receptors for endocannabinoids (eCBs), including n-arachidonic ethanolamide (also called anandamide or AEA) and 2-arachidonic glycerol (2-AG), as well as plant cannabinoids, Such as delta(9)-tetrahydrocannabinol (THC) (PubMed: 15620723, PubMed: 27768894, PubMed: 27851727). Mediates many cannabinoid-induced effects, among other things, it acts on food intake, memory loss, gastrointestinal motility, coma, activity, anxiety, chronic pain. Signaling usually involves the reduction of cyclic AMP. In the hypothalamus, it may have a dual effect on mitochondrial respiration, depending on the dose of the agonist and possibly the cell type. Increase breathing at low doses and decrease breathing at high doses. At high doses, CNR1 signal transduction includes activation of protein g-i and subsequent inhibition of mitochondrial soluble adenylate cyclase, reduction of circulating AMP concentration, and inhibition of protein kinase A (PKA)-dependent mitochondrial electron transport Phosphorylation of specific subunits of the system, including NDUFS2. In the hypothalamus, it inhibits the formation of leptin-induced reactive oxygen species (ROS) and mediates the increase in cannabinoid-induced SREBF1 and FASN gene expression. In response to cannabinoids, it promotes the release of growth-promoting-endorphins from hypothalamic POMC neurons, but does not release the melanocyte-stimulating hormone alpha/alpha-msh, thereby promoting food intake. In the hippocampus, it responds to cannabinoids and regulates cellular respiration and energy production. Participated in cannabinoid-dependent depolarization-induced inhibition (DSI), which is a process in which CA1 postsynaptic pyramidal neurons depolarize and activate eCBs. eCBs retrogradely activate presynaptic CB1 receptors, and transiently lower gaba can inhibit Sexual nerve transmission. It also reduces excitatory synaptic transmission (through similarity). In the superior cervical ganglion and cerebral vascular smooth muscle cells, it inhibits the formation of voltage-gated Ca(2+) channels and an agonist-dependent manner. In cerebral vascular smooth muscle cells, cannabinoid-induced voltage-gated Ca(2+) channel inhibition leads to vasodilation and decreased vascular tone (similar). Induces adipocytes to produce leptin, reduces lrp2-mediated leptin clearance in the kidney, and participates in hyperleptinemia. In adipose tissue, CNR1 signaling pathway leads to increased expression of SREBF1, ACACA and FASN genes (similarity). In the liver, the activation of endocannabinoids leads to increased nascent adipogenesis and decreased fatty acid catabolism, which is associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. It may also affect the synthesis of de novo cholesterol and the intake of hdl-cholesterol ether. Peripheral regulation of energy metabolism (through similarity). In obesity induced by a high-carbohydrate diet, it may reduce the expression of striated muscle mitochondrial dihydrolipid dehydrogenase/DLD and the expression of selected glucose/pyruvate metabolic enzymes, thereby affecting energy expenditure through mitochondrial metabolism (similarity) . In response to the cannabinoid anandamide, it triggers the pro-inflammatory response of macrophages, including the activation of NLRP3 inflammasomes and the secretion of IL1B and IL18 (similar). In the macrophages infiltrating pancreatic islets, this process may be involved in the progression of type 2 diabetes and the loss of related pancreatic cells.
