Cannabinoid receptors, stimulation

CS390 Fox, S. H., M. Kellett, A. P. Moore, A. R. Crossman, and J. M. Brotchie. Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord 2002 17(1) 145-149. 

Selley DE, Stark S, Sim LJ, Childers SR (1996) Cannabinoid receptor stimulation ofguanosine-5 -O-(3-[35S]thio)triphosphate binding in rat brain membranes. Life Sci 59 659-668 Sheskin T, Hanus L, Slager J, Vogel Z, Mechoulam R (1997) Structural requirements for... 

A second mechanism for cannabinoid receptor-mediated stimulation of cyclic AMP production could depend upon which isoform of adenylyl cyclase is expressed in target cells and the way that the particular isoform responds to Gi/o-mediated regulation. Inhibition of adenylyl cyclase by recombinant CBi or (TT receptors was observed in cells that co-express either the isoform 5/6 family or the 1/3/8 family (Rhee et al. 1998) as a result of inhibition by Gi (a subunit). On the other hand, stimulation of adenylyl cyclase was observed in cells coexpressing cannabinoid receptors and the adenylyl cyclase isoform 2/4/7 family, as a result of augmentation of a Gs response by the G y dimers released from Gi due to cannabinoid receptor stimulation (Rhee et al. 1998). 

Vlachou S, Nomikos GG, Panagis G (2003) WIN 55,212-2 decreases the reinforcing actions of cocaine through CBi cannabinoid receptor stimulation. Behav Brain Res 141 215-222... 

Anderson JJ, Kask AM, Chase TN. Effects of cannabinoid receptor stimulation and blockade on catalepsy produced by dopamine receptor antagonists. Eur. J. Pharmacol. 295, 163-168 (1996). 

Two cannabinoid (CB) receptors with about 40 % homology have been identified and cloned to date, namely CBi and CB2. These receptors belong to the superfamily of G-protein coupled membrane receptors [29] and consequently they show a typical heptahelical structure. Interaction with cannabinoid receptors stimulates a cascade of signal transduction pathways, including interaction with potassium and calcium channels (for CBi) and several kinases (e.g., MAP kinase). Since a number of cannabinoid-Uke effects persist in CB1/CB2 knockout mice, the existence of other cannabinoid receptors different from CBi and CB2 has been suggested (e.g., GPR55) [[30], [31]], but their effective role still awaits to be clearly defined. 

Bouaboula, M., Perrachon, S., Milligan, L., Canatt, X., Rinaldi-Carmona, M., Portier, M., Barth, F., Calandra, B., Pecceu, F., Lupker, J., Maffrand, J.-P., Le Fur, G., and Casellas, P. (1997). A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor. J. Biol. Ckem. 272 22330-22339. 

Bouabula MBB, Rinaldi-Carmona M, Shire D, LeFur G, Casellas P. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J Biol Chem 1995b 270 13973-13980. 

Bouabula M, Poinot.-Chazel C, Bourrie B, Canat X, Rinaldi-Carmona M, LeFur G, Casellas P. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 1995a 312 637-641. 

Felder CC, Briley EM, Axelrod J, Simpson JT, Mackie K, Devane WA. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci USA 1993 90 7656-7660. 

The cellular actions of cannabinoids clearly support the proposal that the cannabinoid receptor is inhibitory and, consequently, reduces the firing rate of target neurons. However, this is not wholly confirmed by electrophysiological measurements, which suggest that cannabinoid compounds can stimulate neurons in the hippocampus. This apparent discrepancy may be due to the ability of cannabinoids to inhibit the release of an inhibitory substance in the hippocampus and, thus, produce a net excitation. 

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