An accumulating body of evidence shows that endocannabinoids and cannabinoid receptors

An accumulating body of evidence shows that endocannabinoids and cannabinoid receptors type 1 and 2 (CB1 CB2) play a significant role in physiologic and pathologic processes including cognitive and immune functions. in the setting of neuroinflammation immunomodulation and HIV-1 infection. produces over 80 cannabinoids (Console-Bram et al. 2012 The broader definition of cannabinoids refers to a group of substances that are structurally related to Δ9-tetrahydrocannabinol (Δ9-THC) or that bind to cannabinoid receptors. The chemical definition includes a variety of distinct chemical classes: the classical cannabinoids structurally related to THC the non-classical cannabinoids the aminoalkylindoles the eicosanoids related to the endocannabinoids quinolines and arylsulphonamides (Woelkart et al. 2008 Console-Bram et al. 2012 and additional compounds that do not fall into these standard classes but bind to cannabinoid receptors (CB). Multifaceted effects of marijuana can be designated aiming at evaluation from the potential medical worth of cannabis and cannabinoids in particular human diseases with reduced undesired unwanted effects. Nomenclature of cannabinoid receptors (CB) You can find two well-characterized CB with distinctly different physiological properties. The psychoactive ramifications of cannabinoids are from the CB1 receptor; the CB2 receptor primarily mediates anti-inflammatory and immunomodulatory activities (Miller and Stella 2008 CB1 Cannabinoid receptor 1 (CB1) was found out by Devane et al. in 1988 (Devane et al. 1988 CB1 cDNA was cloned by Matsuda et al. (Matsuda et al. 1990 from rats utilizing a homology method of G-protein-coupled receptors (GPCR). Subsequently CB1 receptors have already been found in additional vertebrates aswell. The genes for mouse rat and human being CB1 receptors (CNR1) can be found on chromosomes 4 5 and 6 respectively. The CB1 receptor can be widely distributed through the entire brain regions specifically the frontal cortex the limbic program like the hippocampus and amygdala sensory and engine Linaclotide areas hypothalamus pons and medulla (Ashton et al. 2007 Ashton and Moore 2011 Human being CB1 stocks 94% amino acidity sequence identification with rodent CB1 (Anday and Mercier 2005 Furthermore Linaclotide to full-length CB1 receptor two splice variations human being CB1a and human being CB1b have already been referred to. Both splice variations have modified ligand Linaclotide binding and activation properties in comparison to complete length CB1 and so are indicated at suprisingly low levels in various cells (Ryberg et al. 2005 On the other hand another group proven no significant variations between your three variants (full-length and two splice-variants) in pharmacological features such as for example binding affinity practical potency and effectiveness of several CB1 agonists (Xiao et al. 2008 The functional significance of different human cannabinoid CB1 receptor variants remains to be clarified. The majority of high CB1-expressing cells are GABAergic (gamma-aminobutyric acid) neurons belonging mainly to the cholecystokinin-positive and parvalbumin-negative type of interneurons (basket cells) and to a less extent to the mid-proximal dendritic inhibitory interneurons. Only a fraction of low CB1-expressing cells is GABAergic. In the hippocampus amygdala and entorhinal cortex areas CB1 mRNA is present at low but significant levels in many non-GABAergic neuronal cells (Marsicano and Lutz 1999 CB2 The second cannabinoid receptor (CB2) was isolated from human myeloid cells in 1992 (Munro et al. 1993 Soon afterwards CB2 was identified in other species such as mouse rat bovine and Linaclotide zebra fish. The CB2 gene is located on chromosome 1 and 4 in humans and mice respectively. Unlike the mouse CB2 gene which is intron-less the human gene has been reported to have two splice variants (Liu Linaclotide et al. 2009 The longer variant human CB2a comprised of exon 1a exon 1b and exon 3 is mostly expressed in testis (about 100-fold more compared to spleen or leukocytes). It is also detected in various regions of the brain Mouse monoclonal to FYN (Liu et al. 2009 The shorter variant human CB2b consisting of exon 2 and exon 3 is expressed mostly in the spleen and leukocytes 100 30 higher respectively when compared to CB2b expression in the brain (Liu et al. 2009 Immune cells express high levels of CB2 and there is a hierarchy of CB2 expression within the immune system (B cells > natural killer cells > monocytes > neutrophils > CD8 lymphocytes > CD4 lymphocytes)(Nunez et al. 2004 Yao and Mackie 2009 The level of expression is dependent on the activation state of the cell and the Linaclotide type of stimuli. Stimulation of splenocytes with LPS.