CBI cannabinoid receptors

Group of compounds which naturally occur in the hemp plant, Cannabis saiiva. Most of them are unsoluble in water. The most abundant cannabinoids are A9--tetrahydrocannabinol (THC), its precursor cannabidiol and cannabinol, which is formed spontaneously from THC. Cannabinoids exert their effects through G-protein coupled cannabinoid receptors (CBi/CB2). 

Initial efforts to identify orphan receptors exploited PCR methodology to clone several novel orphan receptors belonging to the GPCR superfamily. These orphan receptors were subsequently shown to include the adenosine Ai and A2a receptors,a S-HTid receptor,and a central cannabinoid receptor (CBi). PCR using degenerate primers was subsequently used to identify cDNAs encoding the NKi, NK2, dopamine Dj and histamine H3,... 

Clearly there is now incontrovertible evidence for the existence of a mammalian endocannabinoid system that consists of at least two types of cannabinoid receptor, CBi and CB2, and of endogenous agonists (endocannabinoids) for these receptors. Agonists that activate both these receptor types with similar potency or that show marked selectivity for one or other receptor type have been discovered, as have potent CBi- and CB2-selective cannabinoid receptor antagonists. Quantitative and sensitive in vitro and in vivo bioassays for these ligands are also available, and these have played a crucial role in determining the CBi and CB2 receptor affinities and intrinsic activities of a number of cannabinoids. There is good evidence that the endocannabinoid system can become Ionically active and that this is due in some instances to endocannabinoid release and in other instances to the ability of cannabinoid receptors to exist in a constitutively activity state, not only when over-... 

Hillard CJ, Manna S, Greenberg MJ, Dicamelli R, Ross RA, Stevenson LA, Murphy V, Pertwee RG, Campbell WB (1999) Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CBI). J Pharmacol Exp Ther 289 1427-1433... 

Marsicano G, Moosmann B, Hermann H, Lutz B, Behl C (2002) Neuroprotective properties of cannabinoids against oxidative stress role of the cannabinoid receptor CBI. J Neurochem 80 448-456... 

Bouaboula M, Bourrie B, Rinaldi-Carmona M, Shire D, Le Fur G, CaseUas P (1995a) Stimulation of cannabinoid receptor CBI induces krox-24 expression in human astrocytoma cells. J Biol Chem 270 13973-13980... 

Zhuang S, Kittler J, Grigorenko E, Kirby M, Sim L, Hampson R, Childers S, Deadwyler S (1998) Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CBI) mRNA in different rat brain regions. Brain Res Mol Brain Res 62 141-149... 

Marsicano G, Lutz B (1999) Expression of the cannabinoid receptor CBi in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 11 4213-4225... 

Abstract Marijuana and other exogenous cannabinoids alter immune function and decrease host resistance to microbial infections in experimental animal models and in vitro. Two modes of action by whichA -tetrahydrocannabinol (THC) and other cannabinoids affect immune responses have been proposed. First, cannabinoids may signal through the cannabinoid receptors CBi and CB2. Second, at sites... 

Schatz AR, Lee M, Con die RB, Pulaski JT, Kaminski NE (1997) Cannabinoid receptors CBI and CB2 a characterization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol 142 278-287... 

Waksman Y, Olson JM, Carlisle SJ, Cabral GA (1999) The central cannabinoid receptor (CBI) mediates inhibition of nitric oxide production by rat microglial cells. J Pharmacol Exp Ther 288 1357-1366... 

The presence of endocannabinoids has been shown in the hypothalamus (Herkenham 1995) and in the anterior pituitary (Gonzales 1999). The central cannabinoid receptor (CBi receptor) is also present is these structures. The hypothalamus contains fewer cannabinoid binding sites than other areas of the CNS. Nevertheless the effects caused by the activation of CBi receptors in the hypothalamus are important, maybe because the receptors are more or less concentrated within specific hypothalamic nuclei-areas (Fig. 2). CBi receptors seem to be located on intrinsic hypothalamic neurons rather than on neurons with cell bodies located outside the hypothalamus, since hypothalamic deafferentation is not followed by any reduction in the number of cannabinoid receptor binding sites within this brain area (Romero 1998). 

Tissue levels of 2-AG were 10 to 100 times higher than those of anandamide in the same tissue (see Chapter 6). Taken together, it is logical to assume that 2-AG rather than anandamide is the true natural ligand of the cannabinoid receptors (CBi and CBj) (Sugiura et al., 1997, 1999, 2000 for review, Sugiura and Waku 2000). 

Key Words Cannabinoid receptors CBi receptor CB2 receptor electron microscopy immunocytochemistry immunoelectron microscopy immunogold immunohistochemistry immunoperoxidase. 

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