Activation of cannabinoid receptors suppresses neurotransmitter release in various brain regions. In cerebellar Purkinje cells (PCs), cannabinoid agonists suppress both EPSC and IPSC evoked by stimulating the corresponding inputs. However, cannabinoid agonists suppress miniature IPSC (mIPSC) but not miniature EPSC (mEPSC) at normal external Ca2+ concentration ([Ca2+]o). Therefore, cannabinoid a...

Recent studies have suggested that cell migratory responses are often mediated by G(i) protein-coupled receptors. Because it is known that CB1 cannabinoid receptors are coupled to pertussis toxin-sensitive G proteins, we proposed that CB1 may mediate cell migration. To test this hypothesis, modified Boyden chamber assays were used to investigate cell migration mediated by CB1 cannabinoid recept...

The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and th...

Given the vast therapeutic potential of the endocannabinoid system, the revelation of a novel cannabinoid-sensitive target was treated with great excitement. The orphan G-protein coupled receptor 55 (GPR55) was initially touted as a novel cannabinoid target in early industrial patent literature. Consequently, numerous studies have revealed GPR55 expression in a diverse array of cells and tissue...

Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in roden...

Cannabinoids enhance the function of glycine receptors (GlyRs). However, little is known about the mechanisms and behavioral implication of cannabinoid-GlyR interaction. Using mutagenesis and NMR analysis, we have identified a serine at 296 in the GlyR protein critical for the potentiation of I(Gly) by Δ(9)-tetrahydrocannabinol (THC), a major psychoactive component of marijuana. The polarity of...

A set of 29 3-alkyl 5-arylimidazolidinediones (hydantoins) with affinity for the human cannabinoid CB(1) receptor was studied for their lipophilicity and conformational properties in order to delineate a pharmacophore. These molecules constitute a new template for cannabinoid receptor recognition, since (a) their structure differs from that of classical cannabinoid ligands and (b) antagonism is...

Emerging data suggest that off-target cannabinoid effects may be mediated via novel seven-transmembrane spanning/G protein-coupled receptors. Due to its cannabinoid sensitivity, the G protein-coupled receptor 55 (GPR55) was recently proposed as a candidate; however, GPR55 is phylogenetically distinct from the traditional cannabinoid receptors, and the conflicting pharmacology, signaling, and fu...

The endocannabinoid system plays a physiological natural anti-inflammatory anticancer role and the pharmacological effects of cannabinoids from Cannabis plant simply reflect action endogenous ones. Therefore, therapeutic point view cannot be understood without taking into consideration physio-pathological system. Despite great number potentially molecules with plant, they may synthetized within...

Current cannabinoid research is based on a number of major discoveries made by Professor Raphael Mechoulam. In the mid-1960s, he, together with Professor Yechiel Gaoni, identified in the plant Cannabis sativa, the psychoactive component of marijuana and hashish, D-tetrahydrocannabinol (THC), determined its chemical structure (Gaoni and Mechoulam, 1964; Mechoulam and Gaoni, 1967) and synthesized...