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By Roger G. Pertwee

There's at the moment substantial curiosity within the improvement of medications that might increase endocannabinoid-induced “autoprotection”, for instance via inhibition of endocannabinoid metabolizing enzymes or mobile uptake strategies or that might oppose endocannabinoid-induced “autoimpairment”. This quantity describes the body structure, pathophysiology and pharmacology of the endocannabinoid approach and power innovations for concentrating on the program within the medical institution.

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Biochem Mol Biol Int 40:931–938 Sun Y, Alexander SPH, Garle MJ, Gibson CL, Hewitt K, Murphy SP, Kendall DA, Bennett AJ (2007) Cannabinoid activation of PPARα; a novel neuroprotective mechanism. Br J Pharmacol 152:734–743 Tao Q, Abood ME (1998) Mutation of a highly conserved aspartate residue in the second transmembrane domain of the cannabinoid receptors, CB1 and CB2, disrupts G-protein coupling. J Pharmacol Exp Ther 285:651–658 T oth BI, Dobrosi N, Dajnoki A, Czifra G, Ola´h A, Sz€ollosi AG, Juha´sz I, Sugawara K, Paus R, Bı´ro T (2011) Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1.

2005)d Bouaboula et al. (2005) and Rockwell et al. (2006) Ghosh et al. (2007) GPCR G protein-coupled receptor, TRP transient receptor potential, PPAR peroxisome proliferator-activated receptor. See Fig. 1 legend for definitions of other abbreviations a Displacement of a radioligand from a binding site b 1–10 μM, for an effective concentration, EC50 or IC50 c >10–100 μM, for an effective concentration, EC50 or IC50 d See review by Pertwee et al. (2010) e Possible negative allosteric modulation f Agonism g Unspecified μM, for an effective concentration, EC50 or IC50 h Potentiation of γ-aminobutyric acid i Inhibition or antagonism Endocannabinoids and Their Pharmacological Actions 21 antagonism is non-competitive, and hence possibly allosteric, in nature.

J Mol Neurosci 13:55–61 Lauckner JE, Jensen JB, Chen H-Y, Lu H-C, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A 105:2699–2704 Leggett JD, Aspley S, Beckett SRG, D’Antona AM, Kendall DA, Kendall DA (2004) Oleamide is a selective endogenous agonist of rat and human CB1 cannabinoid receptors. Br J Pharmacol 141:253–262 Li Q, Ma H-J, Song S-L, Shi M, Ma H-J, Li D-P, Zhang Y (2012) Effects of anandamide on potassium channels in rat ventricular myocytes: a suppression of Ito and augmentation of KATP channels.

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