Endocannabinoid anandamide

Endocannabinoids. Figure 1 Chemical structures of the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, of Cannabis sativa psychoactive principle, A9-tetrahydrocannabinol, and of the CB-i receptor antagonist/inverse agonist, rimonabant. 

Endocannabinoids (anandamide, 2-arachidonylglyerol Widely distributed CB1 WIN55212-2 methylester SR141716 Inhibitory (presynaptic) 4 Ca2+ conductance, 1 cAMP... 

Okamoto K, Beieiter DF, Thompson R, TasMro A, Bereiter DA (2008) Estradiol replacement modifies c-fos expression at the spinomedullary junction evoked by temporomandibular joint stimulation in ovariectomized female rats. Neuroscience 156 729-736 Okamoto Y, Wang J, Morishita J, Ueda N (2007) Biosynthetic pathways of the endocannabinoid anandamide. Chem Biodivers 4 1842-1857... 

Figure 10.6. The biosyntliesis of endocannabinoids. Biosyntlietic patliways for tlie biosyntliesis of tire major endocannabinoids anandamide and 2-aiachidonoylglycerol (2-AG). Note drat die enzymes N-acylUansferase in anandamide biosyndiesis. Tire biosyndiesis of 2-AG can proceed via two different routes and is also dependent on an increase in Ca +. Figures reprinted from Piomelli (2003) widi permission from Nature Publishing Group.

Kozak KR, Piusakiewicz JJ, Rowhnson SW, Pmdhomme DR, Marnett LJ (2003) Amino acid determinants in cyclooxygenase-2 oxygenation of the endocannabinoid anandamide. Biochemistry 42 9041-9049 Kurahashi Y, Ueda N, Suzuki H, Suzuki M, Yamamoto S (1997) Reversible hydrolysis and synthesis of anan-... 

Rueda D, Navarro B, Martinez-Serrano A, Guzman M, Galve-Roperh 1 (2002) The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation through attenuation of the Rapl/B-Raf/ERK pathway. J Biol Chem 277 46645-46650... 

Fig. 2. Major biosynthetic pathways and enzymes for the endocannabinoid anandamide (AEA) and other W-acylethanolamines. The circled P indicates a phosphate group. N-ArPE, W-arachidonoyl-phosphatidylethanolamine PE, phosphatidylethanolamine PLD, phospholipase D sPLA.2, secretory phospholipase Az of group IB...

Fowler CJ, Tiger G, Lopez-Rodriguez ML, Viso A, Ortega-Gutierrez S, Ramos JA (2003) Inhibition of fatty acid amidohydrolase, the enzyme responsible for the metabolism of the endocannabinoid anandamide, by analogues of arachidonoyl-serotonin. J Enzyme Inhib Med Chem 18 225-231... 

Maingret F, Patel AJ, Lazdunski M, Hon ore E (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K(-t) channel TASK-1. EMBO J 20 47-54... 

Another interesting member of the TRP channel family that has been characterised recently is ANKTMl, which is activated byA -tetrahydrocannabinol as well as being implicated in the detection of noxious cold (Jordt et al. 2004). However, the physiological relevance of the effect of A -tetrahydrocannabinol on ANKTMl is unclear because the endocannabinoids anandamide and 2-AG do not activate this TRP channel (Jordt et al. 2004). Nevertheless, it is possible that other as-yet-unidentified endocannabinoids act as endogenous ligands for ANKTMl. 

Finally, cannabinoids inhibit the release of neuropeptides like calcitonin gene-related peptide (CGRP), substance P and somatostatin from sensory neurons (Table 4). Capsaicin or electrical stimulation was used to evoke neuropeptide release. In some of these studies, the endocannabinoid anandamide was used, which has a dual effect on neuropeptide release from sensory neurons. Anandamide possesses an inhibitory effect mediated via CBi receptors at low concentrations and... 

In addition to their short-term effects, cannabinoids also modulate the induction of long-term synaptic plasticity. Administration of THC and the endocannabinoids anandamide and 2-AG inhibits the induction of long-term potentiation (LTP) in the hippocampus (Nowicky et al. 1987 Terranova et al. 1995 Stella et al. 1997) and long-term depression (LTD) within the cerebellum and nucleus accumbens (Levenes et al. 1998 Hoffman et al. 2003a). 

Endocannabinoids Anandamide Immobility and decreased rearing behavior in rodents (Fride and Mechoulam 1993 Crawley etal. 1993 Smith etal. 1994) Reduction of ambulation and stereotypy, and increase of inactivity in rats (as with zl -THC, but its effects were of shorter duration) (Romero et al. 1995a and 1995b) Potentiation of muscimol-induced catalepsy (Wickens and Pertwee 1993) Turning behavior at low doses in mice (Souilhac etal. 1995)... 

In contrast to the growing knowledge on the vascular effects of cannabinoids, little is known about cannabinoid-induced direct cardiac effects. The endocannabinoid anandamide (Felder et al. 1996), anandamide amidohydrolase (Bilfinger et al. 1998), and traces of the message for the CBi receptor (Galiegue et al. 1995) have all been detected in the human heart. In a more recent study, the existence of CBi receptors was confirmed in human atrial myocytes by immunoblotting and immunohistochemistry (Bonz et al. 2003). In the same study, it was demonstrated... 

Cannabinoids, the active components of Cannabis sativa and their derivatives, act in organisms by mimicking endogenous substances—the endocannabinoids anandamide and 2-arachidonoylglycerol—that bind to and activate specific cannabinoid receptors. So far, two cannabinoid-specific Gj/o protein-coupled receptors, CBl (Matsuda et al. 1990) and CB2 (Munro et al. 1993), have been cloned and characterised from mammalian tissues. Most of the effects of cannabinoids rely on CBi receptor activation. This receptor is particularly abundant in discrete areas of the brain, but is also expressed in peripheral nerve terminals and various extra-neural sites such as testis, eye, vascular endothelium and spleen. In contrast, the CB2 receptor is almost exclusively present in the immune system (Howlett et al. 2002). 

Jonsson KO, Vandevoorde S, Lambert DM, Tiger G, and Fowler CJ (2001) Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br J Pharmacol 133 1263-75. 

Wenger, T., Gerendai, I., Fezza, E, Gonzalez, S., Bisogno, T., Fernandez-Ruiz, J., and Di Marzo, V. (2002) The hypothalamic levels of the endocannabinoid, anandamide, peak immediately before the onset of puberty in female rats, Life Sciences 70 1407-1414. Erratum Life Sciences 71 1349-1350. 

---