Use of Cannabinoids as a NoveL Therapeutic Modality Against Autoimmune Hepatitis

Hegde,* Narendra P. Singh,* Lome Hofseth Uday Singh,* Swapan Ray,* Mitzi Nagarkatti,* and Prakash S. Nagarkatti* II. The Endogenous Cannabinoid System 489 III. The Biosynthesis of Endocannabinoids 490 IV. Endocannabinoid System is Autoprotective 490 A. The endocannabinoid system and pathophysiology of liver diseases 490 B. Anti-inflammatory effects of endocannabinoids 492 V. Autoimmune Hepatitis 492 VI. Treatment Drawbacks 494 System in Hepatitis 494 A. Controversies...

Histo RicaL View of Lipid Signaung Discoveries

The use of natural products for a variety of ailments in folklore medicine attracted scientists to explore their mechanisms of bioactivity (Caterina et al., 1997 Mechoulam and Gaoni, 1965 Naef et al., 2003 Urca et al., 1977). The finding that plant-derived active ingredients such as the opium-derived morphine and cannabis-derived D9-hydrotetracannabinol (D9-THC cannabinoids) that had a wide range of biological activity promoted the identification ofnovel endogenous cannabinoid-like signaling...

Pharmacology of GPR55

The two patents clearly showed that GPR55 binds to, and is activated by, a variety of cannabinoid ligands but aspects of its pharmacology are not consistent with it being the receptor which mediates all, if any, of the functional effects ascribed to actions of anandamide and other cannabinoids at receptors other than the classical CB1 and CB2 types. More recently, Johns et al. (2007), from GlaxoSmithKline, confirmed that abnormal cannabidiol and 0-1602 activated GTPgS binding in HEK293T cells...

C CB1 Receptormediated regulation of ion channels 1 Calcium channels

Anandamide has been demonstrated to modulate calcium channels through a range of pathways. Calcium spikes typical of cultured rat hippocampal neurons stimulated with glutamate are inhibited by anandamide with an IC50 of 71 nM (Shen et al., 1996). In cerebellar granule cells methananda-mide increased Ca2+ elevations induced by stimulation with glutamate and high K+. This effect was CB1 receptor dependent and occurred through activation of phospholipase C (PLC) and inositol triphosphate (IP3)...

Apoptosis A ModeL for the Mechanism and Regulation of Oleamide Biosynthesis

The fundamental importance of apoptosis in normal embryogenesis and adult tissue remodeling is well recognized (Danial and Korsmeyer, 2004 Rathmell and Thompson, 2002 Thompson, 1995 Yuan and Yankner, 2000). The ability of cytochrome c to catalyze the synthesis of oleamide has intriguing implications in this process. Central to this apoptosis is the release of cytochrome c from mitochondria which triggers the Figure 3.7 Mechanistic model for the roles of cytochrome c, oleamide, and gap junctions...

I

Figure 18.1 Schematic diagram of the cannabinoid receptor-dependent mechanisms whereby AEA leads to tumor growth suppression and or cell death. AEA may act via the Cb1 receptor to activate the cAMP PKA MAPK pathway or to increase the production of ceramide. These effects ultimately result in a decrease in the expression of various growth factor receptors and decrease cell cycle progression. Alternatively, AEA may activate either Cb2 or VR1 to elicit a similar response, although the mechanism by...

Cannabinoid Receptor Expression in Neutrophils

Derocq et al. (2000) conducted studies with wild type and differentiated HL-60 cells, which, as previously mentioned, are derivative of committed neutrophil progenitors of the granulocyte monocyte lineage (Gallagher et al., 1979), they observed a dramatic decrease of CB2 receptor mRNA transcripts during the course of DMSO-induced differentiation, implying a downregulation of the expressed CB2 receptor. Deusch et al. (2003) were also unable to find any CB2...

The preimplantation embryo and implantation Critical role for the ECS system

The ECS system has been detected in virtually all components of the reproductive system and at virtually all stages of fertilization and development (Maccarrone and Finazzi-Agro, 2004 Schuel and Burkman, 2005). Thus for example, cannabinoid receptors and anandamide have been detected in sperm cells from sea urchins as well as humans and other species. Anandamide may be released from sea urchin egg cells, when it is postulated to modulate the rate of their fertilization by the sperm. This...

Coordination of GCMediated Control of the Neuroimmune Response and Energy Homeostasis Control

Both basal and stress-related homeostasis is centrally coordinated by the sympathoadrenomedullary system (SAS), and by the HPA axis. When homeostasis is disturbed or threatened by immune challenge or by some stressors both the SAS and HPA axis become centrally activated, resulting in increased release of catecholamines from the adrenal medulla and peripheral sympathetic terminals, and increased GCs release from the adrenal cortex (Elenkov et al., 2000). In the periphery, the HPA axis is...

O1918

Inactive WIN55212, other cannabinoids Not tested LPI Figure 5-4 Different ligand specificities for GPR55 showing the three signaling modalities that have been reported. See text for explanation. specificity that have been described are summarized in Fig. 5.4 as three signaling modalities. In the first modality, AM251 and LPI behave as agonists which are antagonized by CP55,940, and signaling downstream of GPR55 is mediated via Ga13. This pattern of ligand specificity has been observed in yeast...

Regulation of TRPVi responsiveness to anandamide

In general, the in vivo activity of TRPV1 appears to be dependent on its sensitization state. There are numerous mechanisms identified which regulate TRPV1 activity. One of the most studied pathways is the phosphorylation ofTRPVl, which affects its sensitivity to vanilliods and to anandamide Fig. 15.2 . TRPV1 is phosphorylated on serine and threonine residues by protein kinase C PKC Bhave et al., 2003 Premkumar and Ahern, 2000 PKA Bhave et al., 2002 , protein kinase D Wang et al., 2004 , and...

Cannabinoids Modulate Cell Migration

As CB1 and CB2 receptors couple to pertussis toxin-sensitive Gi o-proteins, it was theorized that these receptors may be involved in cell migration. Subsequent studies have indeed shown that Gi o proteincoupled receptors, including CB1 and CB2, modulate cell migration Derocq et al., 2000 Song and Zhong, 2000 Walter et al., 2003 . Song and Zhong found that the cannabinoid agonists HU-210, WIN55212-2, and AEA are able to induce chemotaxis and chemokinesis stimulated random motion , via the CB1...