Novel Pharmacological Targets for Cannabinoids

R.   G.   Pertwee

doi:10.2174/1570159043476927

Abstract

There is convincing evidence that mammalian tissues express at least two types of cannabinoid receptor, CB1 and CB2, and that the endogenous cannabinoid, anandamide, and certain other eicosanoid agonists for known cannabinoid receptors can also activate vanilloid (VR1) receptors. Evidence is now also emerging that in addition to these established receptors for cannabinoids, other pharmacological targets for eicosanoid and / or non-eicosanoid cannabinoids are present in neuronal or non-neuronal tissues that include brain, spinal cord, microglial cells, heart, certain arteries, small intestine, vas deferens and peritoneum. Among new receptors to have been proposed for cannabinoids are CB2-like receptors in mouse paw and peritoneum, receptors for abnormal-cannabidiol in microglial cells and in arterial endothelial and non-endothelial cells, Gprotein coupled receptors for R-(+)-WIN55212 and anandamide in brain and spinal cord, receptors for Δ9- tetrahydrocannabinol and cannabinol on perivascular sensory nerves, α2-adrenoceptor-like (imidazoline) receptors at sympathetic nerve terminals and VR1-like receptors on glutamatergic neurons in hippocampus and dentate gyrus. The presence of novel allosteric sites for cannabinoids on delayed rectifier potassium channels and on 5-HT3, muscarinic M1 and M4, and glutamate GLUA1 and GLUA3 receptors has also been proposed. Current evidence for the existence of these new molecular targets for cannabinoids is summarized in this review. This evidence is largely pharmacological in nature, much of it coming from functional or binding assays with established or novel ligands, sometimes performed using tissues or cell lines that do not express CB1 or CB2 receptors. None of the proposed new cannabinoid receptors have yet been cloned.

Keywords: Pharmacological, CB1 and CB2, muscarinic, GLUA1 and GLUA3, hippocampus, Gprotein

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