Signal transduction, cannabinoids

Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Mitchell RL. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 1995 48 443-449. 

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. 

Wartmann M, Campbell D, Subramanian A, Burstein SH, Davis RJ (1995) The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide. FEBS Lett 359(2-3) 133-6... 

Berrendero, F., Garcia-Gil, L., Hernandez, M. L., Romero, J., Cebeira, M., de Miguel, R., Ramos, J. A., and Femandez-Ruiz, J. J. (1998). Localization of mRNA expression and activation of signal transduction mechanisms for cannabinoid receptor in rat brain during fetal development. Development 125, 3179—3188. 

Mato, S., Del Olmo, E., and Pazos, A. (2003). Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain. Eur. J. Neurosci. 17, 1747-1754. 

Childers SR, Pacheco MA, Bennett BA, Edwards TA, Hampson RE, et al. 1993. Cannabinoid receptors G-protein-mediated signal transduction mechanisms. Bio-chem Soc Symp 59 27-50. 

Since our 1987 review, there has been enormous progress in our understanding of the biochemical basis of cannabinoid action - receptors were identified, endogenous cannabinoids were isolated, and their structures were elucidated. The signalling transduction mechanisms involved have been the object of numerous studies. In the present review, we shall try to... 

These developments have been described and discussed in the reviews cited above which should be consulted for details, in particular as regards molecular biology, signal transduction mechanisms, pharmacological and physiological implications of the discovery of cannabinoid receptors [5-15],... 

Breivogel CS, Childers SR (2000) Cannabinoid agonist signal transduction in rat brain comparison of cannabinoid agonists in receptor binding, G-protein activation, and adenylyl cyclase inhibition. J Pharmacol Exp Ther 295 328-336... 

Cannabinoid Receptor-Mediated Signal Transduction to the Nucleus. 61... 

Abstract The cannabinoid receptor family currently includes two types CBi, characterized in neuronal cells and brain, and CB2, characterized in immune cells and tissues. CBi and CB2 receptors are members of the superfamily of seven-transmembrane-spanning (7-TM) receptors, having a protein structure defined by an array of seven membrane-spanning helices with intervening intracellular loops and a C-terminal domain that can associate with G proteins. Cannabinoid receptors are associated with G proteins of the Gi/o family (Gil,2 and 3, and Gol and 2). Signal transduction via Gi inhibits adenylyl cyclase in most tissues and cells, although signaling via Gs stimulates adenylyl cyclase in some experimental models. Evidence exists for cannabinoid receptor-mediated Ca fluxes and stimulation of phospholipases A and C. Stimulation of CBi and CB2 cannabinoid... 

Cannabinoid receptor agonists stimulate the production and release of nitric oxide (NO) by a CBi receptor-mediated mechanism utilizing one of the NO synthase (NOS) isoforms in neuronal tissues and model cells (see Fimiani et al. 1999a for review). The signal transduction pathway between CBi receptors and neuronal NOS (nNOS) regulation is believed to be important for mediating the effects of A -THC on hypothermia and locomotor activity (but not antinociception), as determined by the absence of these responses in nNOS (-/-) knock-out mice (Azad et al. 2001). NO production was stimulated by anandamide via SR141716-sensitive CBl receptors in rat median eminence shces, but it was not clear from these studies... 

Chronic exposure to /I -THC and other cannabinoid receptor agonists generally leads to biological adaptive mechanisms that may be related to the phenomenon of tolerance. Cellular modifications in response to chronic agonist stimulation have included cannabinoid receptor down-regulation, as well as desensitization of signal transduction pathways. These effects have been recently reviewed in detail (Sim-Selley 2003). 

The CBl and CBj cannabinoid receptors in nervous, immune, and other tissues of the body participate in G protein-mediated signal transduction pathways. Particularly well characterized are those that regulate the second messengers cyclic AMP, Ca ", and perhaps IP3. CBi receptors are modulators of ion channels, which makes them key players in the control of neurotransmission. These receptors also partic-... 

Felder CC, Veluz JS, Williams HL, Briley EM, Matsuda LA (1992) Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones. Mol Pharmacol 42 838-845... 

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