Journal ArticleDOI
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
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TLDR
The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.Abstract:
Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.read more
Citations
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Journal ArticleDOI
The cloning of a family of genes that encode the melanocortin receptors
TL;DR: The murine and human MSH receptors (MSH-Rs) and a human ACTH receptor (ACTH-R) were cloned and define a subfamily of receptors coupled to guanine nucleotide-binding proteins that may include the cannabinoid receptor.
Journal ArticleDOI
Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.
TL;DR: The results generally agree well with the previous studies using CB1 receptor autoradiography and messenger RNA in situ hybridization, but because of its greater resolution, immunohistochemistry allowed identification of particular neuronal cells and fibers that possess cannabinoid receptors.
Journal ArticleDOI
Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses.
Rachel Wilson,Roger A. Nicoll +1 more
TL;DR: The transient suppression of GABA-mediated transmission that follows depolarization of hippocampal pyramidal neurons is mediated by retrograde signalling through release of endogenous cannabinoids, indicating that the function of endogenous cannabinoid released by depolarized hippocampal neurons might be to downregulate GABA release.
Journal ArticleDOI
Role of Endogenous Cannabinoids in Synaptic Signaling
TL;DR: The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation, and the fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release.
Journal ArticleDOI
Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study
TL;DR: CB1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over 1 year, promoted significant decrease of bodyweight and waist circumference, and improvement in cardiovascular risk factors.
References
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Cannabinoid receptor localization in brain
TL;DR: The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in the in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience.
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G proteins and dual control of adenylate cyclase
TL;DR: It is clear that detailed understanding of the mechanism of regulation of CAMP synthesis will soon be achieved from study of the interactions of purified components that have been reconstituted in lipid bilayers of defined composition.
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Identification of a family of muscarinic acetylcholine receptor genes
TL;DR: Analysis of human and rat genomic clones indicates that there are at least four functional muscarinic receptor genes and that these genes lack introns in the coding sequence.