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Structure of a Cannabinoid Receptor and Functional Expression of the Cloned Cdna

Authors:
  • Azevan Pharmaceuticals

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.

Supplementary resource (1)

... ∆ 9 -Tetrahydrocannabinol (∆ 9 -THC) is one of the major active substances of marijuana [1]. Most of the pharmacological actions of ∆ 9 -THC have been shown to be mediated by two types of G-protein-coupled receptors (GPCRs), CB1 and CB2 receptors [2,3]. These receptors share 44% overall identity (68% identity for the transmembrane domains). ...
... GPR55 was proposed to function as a cannabinoid receptor [13,14,[17][18][19][20][21]. Of note, GPR55 2 of 13 has low sequence identity with the CB1 receptor (13.5%) and the CB2 receptor (14.4%), respectively [2,3,8,13]. ...
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