CNR1 Protein-VLP, Human (T210A, HEK293)

The CNR1 Protein-VLP serves as a G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids like delta(9)-tetrahydrocannabinol (THC). It mediates a range of cannabinoid-induced effects on food intake, memory, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, and chronic pain, typically involving a reduction in cyclic AMP. In the hypothalamus, it exhibits a dual effect on mitochondrial respiration, increasing respiration at low doses and decreasing it at high doses through G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase. Additionally, CNR1 inhibits leptin-induced reactive oxygen species (ROS) formation, mediates cannabinoid-induced increases in SREBF1 and FASN gene expression, and drives the release of orexigenic beta-endorphin from hypothalamic POMC neurons. In the hippocampus, it regulates cellular respiration and energy production in response to cannabinoids and is involved in cannabinoid-dependent processes like depolarization-induced suppression of inhibition (DSI). CNR1 also inhibits voltage-gated Ca(2+) channels in superior cervical ganglions and cerebral vascular smooth muscle cells, leading to vasodilation and decreased vascular tone. It induces leptin production in adipocytes, reduces LRP2-mediated leptin clearance in the kidney, and modulates lipid metabolism in adipose tissue and the liver. Furthermore, CNR1 peripherally modulates energy metabolism and, in obesity induced by a high carbohydrate diet, may affect mitochondrial dihydrolipoyl dehydrogenase/DLD expression in striated muscles and selected glucose/pyruvate metabolic enzymes. In response to cannabinoid anandamide, CNR1 elicits a pro-inflammatory response in macrophages, potentially contributing to the progression of type-2 diabetes and the loss of pancreatic beta-cells. Notably, CNR1 binds both 2-arachidonoylglycerol (2-AG) and anandamide.