Abstract
Membrane environment and endocannabinoid signaling
Highlights
CB1 receptor is the most abundant G protein-coupled receptor (GPCR) in the brain (Howlett et al, 2010)
Together with its endogenous agonists (AEA, 2-AG, and other congeners), CB1 belongs to an ancient neurosignaling system that plays important control functions within the central nervous system (Katona and Freund, 2008)
I would like to comment that subtle, yet specific, differences might underpin the differential sensitivity of CB1 and CB2 to membrane cholesterol, possibly explaining the apparent redundancy of having two largely overlapping receptor subtypes that are activated by similar compounds and trigger similar transduction pathways: (i) inhibition of adenylyl cyclase, (ii) regulation of ionic currents, and (iii) activation of focal adhesion kinase, mitogen-activated protein kinase, and cytosolic phospholipase A2 (Di Marzo, 2009; Maccarrone et al, 2010)
Summary
CB1 receptor is the most abundant G protein-coupled receptor (GPCR) in the brain (Howlett et al, 2010). It has become evident the involvement of membrane lipids, especially cholesterol and glycosphingolipids, in regulating the function of GPCRs like β2-adrenergic and serotonin1A receptors, as well as of several other membrane-associated proteins like caveolins (Pontier et al, 2008; Prinetti et al, 2009; Paila et al, 2010; Shrivastava et al, 2010).
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