Nervous system, endocannabinoids

Endocannabinoids are endogenous mediators acting via the binding to, and activation of, cannabinoid receptors, CBX and CB2 [1]. iV-arachidonoy 1-ethanol-amine (AEA, anandamide) and 2-arachidonoyl-glycerol (2-AG) (Fig. 1) are the two most studied endocannabinoids. In the nervous system, endocannabinoids act as... 

Porter, A.C. and Felder, C.C. (2001) The endocannabinoid nervous system unique opportunities for therapeutic intervention. Pharmacology el Therapeutics, 90 (1), 45—60. 

Manzoni. Endocannabinoids in the central nervous system Med Sci (Paris) CS316... 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1997) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neurosci 83(2) 393 411 Van Beugen BJ, Nagaraja RY, Hansel C (2006) Climbing fiber-evoked endocannabinoid signaling heterosynaptically suppresses presynaptic cerebellar long-term potentiation. J Neurosci 26(32) 8289-94... 

Ahn, K., McKinney, M., and Cravatt, B. (2008). Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem. Rea. 108, 1687-1707. 

Matias I, Bisogno T, Melck D, Vandenbulcke F, Verger-Bocquet M, De PetroceUis L, Sergher-aert C, Breton C, Di Marzo V, Salzet M (2001) Evidence for an endocannabinoid system in the central nervous system of the leech Hirudo medicinalis. Brain Res Mol Brain Res 87 145-159... 

The in vivo cardiovascular effects of carmabinoids are complex and may involve modulation of the autonomic outflow in both the central and peripheral nervous systems as well as direct effects on the myocardium and vasculature. However, their peripheral actions appear to play the dominant role, at least upon systemic administration at the doses used by most investigators. Moreover, the effects of endocannabinoids are complicated by their rapid metabolism, which may liberate other vasoactive substances and their precursors (reviewed in Mechoulam et al. 1998 Kunos et al. 2002 Randall et al. 2002 Ralevic et al. 2002). 

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