Cannabinoid receptor expression

Mato, S., Del Olmo, E., and Pazos, A. (2003). Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. Eur. J. Neurosci. 17, 1747-1754. 

Using in situ radioligand binding, another study reported an increased CB1 density in DLPFC, an effect that was not dependent on previous cannabis use (Dean et al., 2001). In addition, an increased CB1 receptor density in the striatum has been reported, which may have been associated with recent cannabis intake (Dean et al., 2001). Postmortem studies of cannabinoid receptor expression, in particular for the CB1 receptor in PCC, ACC and DLPFC support the involvement of the cannabinoid system in the pathophysiology of schizophrenia. 

There is increasing evidence to support a role for peripheral CB2 receptors in the analgesic effects of cannabinoids. Thus, chronic pain induced by peripheral nerve injury, but not that produced by peripheral inflammation, was associated with the enhancement of CB2 cannabinoid receptor expression, specifically located in the lumbar spinal cord (Malan et al. 2002). Thus, a selective induction of spinal CB2 expression presumably occurs on activated microglia in regions undergoing neuronal damage. 

Soderstrom K, Johnson F (2000) CBl cannabinoid receptor expression in brain regions associated with zebra finch song control. Brain Res 857 151-157... 

Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide hydrolase and cb(l) cannabinoid receptor expression in the mouse brain evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119 481-496... 

Bouaboula M, Rinaldi M, Carayon P, Carillon C, Delpech B, Shire D, Le Fur G, Casellas P (1993) Cannabinoid-receptor expression in human leukocytes. Eur J Biochem 214 173-180... 

Wright K, Rooney N, Tate J, et al (2003) Functional cannabinoid receptor expression in human colonic epithelium. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 25... 

Develop with Hanker-Yates reagent Development usually is complete by 15 min. However, intensity of development may vary depending on the primary antibody used and the amount of cannabinoid receptor present in tissue. A general approach is to place a negative control (e.g., cells on a cover slip treated with normal rabbit IgG as the primary antibody) side by side with a positive control (e.g., cells transfected with a cannabinoid receptor expression construct). The development reaction is terminated when the positive control qualitatively exhibits a twofold level of staining at the macroscopic level. Alternatively, the staining reaction can be monitored under an inverted cell culture microscope. 

Matsuda LA, Lolait SJ, Brownstein MJ, et al Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 364 561—564, 1990... 

Nowell KW, Pettit DA, Cabral WA, et al High-level expression of the human CB2 cannabinoid receptor using a baculovirus system. Biochem Pharmacol 55 1893— 1905, 1998... 

Mouse vas deferens (MVD) seems to express CB1 and at least one CB2-like cannabinoid receptor type, as is demonstrated by the presence of CB1 and CB2-like mRNA as well as by data collected from experiments with cannabinoid receptor selective agonists and antagonists (Pertwee, 1999). Furthermore, evidence indicates that a CBl-like receptor exists in vascular endothelium, which upon activation produces significant hypotension (Wagner, 1999). This receptor differs from CB1 in its pharmacological response to some well-characterized cannabimimetics. 

Bouabula MBB, Rinaldi-Carmona M, Shire D, LeFur G, Casellas P. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J Biol Chem 1995b 270 13973-13980. 

Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA 1995 92 3376-3380. 

Gerard, CM, Molerau, C, Vassart, G, Parmentier, M. Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 1991 279 129-134. 

Cannabinoid receptors are expressed throughout the cerebral cortex and the hippocampus, and a subpopulation of these cells appear to show an unusually high level of activity. It is possible that cells in these areas modulate the sensory effects of cannabis, particularly the effects on perception, task performance and memory. In addition, the anticonvulsant properties of cannabis are believed to be mediated here. Parts of the hypothalamus show high levels of receptor sites for cannabinoids this may be related to hypothermia effects. High levels in the cerebellum may be related to mediating the property of cannabinoids that produces the reduction in ataxic (muscle co-ordination) symptoms in certain disorders (Herkenham et al., 1991). 

Zhuang S, Kittler J, Grigorenko EV, Kirby MT, Sim U, Hampson RE, Childers SR, Deadwyler SA. (1998). Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CBl) mRNA in different rat brain regions. Brain Res Mol Brain Res. 62(2) 141-49. 

The endocannabinoid system might also be involved, since A9-tetrahydorcan-nabinol, the major active ingredient in cannabis, decreases somatically expressed withdrawal behaviors and the aversiveness of withdrawal in mecamylamine- and naloxone-precipitated nicotine abstinence (Balfour 2002). However, genetic knockout of the CBl cannabinoid receptors did not significantly affect somatically expressed withdrawal behaviors (Castane et al. 2002). 

In 1988, the same group reported the existence of a cannabinoid receptor in rat brain. High affinity and stereoselectivity — essential criteria for a pharmacologically distinct cannabinoid receptor — in the brain was demonstrated. Several years later, the cDNA of the cannabinoid receptor was isolated from a rat cerebral cortex cDNA library and expressed in Chinese hamster ovary cells.This G-protein-coupled receptor was isolated from a human brain stem cDNA library. The deduced amino acid sequence encoded a protein of 472 residues, which shares 97.3% identity... 

A peripheral cannabinoid receptor was cloned from HL-60 cells. It is not expressed in the brain but in macrophages in the marginal zone of spleen. The peripheral cannabinoid receptor, mCB2, was cloned from a mouse splenocyte cDNAUbrary. This protein of347 residues shares 82% overall identity with the only other known peripheral receptor, human CB2 (hCB2) and is shorter by 13 amino acids at the C-terminus. 

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