Anandamide oxidation products

Fig. 3 Enzymatic oxidation of endocannabinoids. The oxidation of anandamide and 2-AG has been suggested to occur through the catalytic action of either cyclooxygenase-2 or 12- and 15-lipoxygenases. The oxidation products of the former, but not latter, reaction are totally inactive on cannabinoid receptors, but may bind to yet-to-be-identified receptors...

Stefano GB, Salzet B, Rialas CM, Pope M, Kustka A, Neenan K, Pryor S, Salzet M (1997a) Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic dopamine release. Brain Res 763 63-68... 

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... 

Other metabolic routes involve oxidative transformations that bear close resemblance to the processes that lead to the eicosanoids (Kozak et al., 2000 Kozak, Crews, et al., 2001 Kozak, Prusakiewicz, et al., 2001 Kozak, Crews, et al., 2002 Kozak and Mamett, 2002). For example, both 12- and 15-lipoxygenase products of anandamide are known (Edgemond et al., 1998 Moody et al., 2001 Kozak, Gupta, et al., 2002), as well as a group of P-450-mediated hydroxy anandamide metabolites (Bomheim et al., 1993 Bomheim et al., 1995). Free arachidonic acid is required for COX-1-mediated conversion to PGs, whereas the requirements for COX-2-mediated conversion... 

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