Interaction of endocannabinoid receptors with biological membranes.

Abstract:

:Cellular signaling is regulated by several biochemical reactions, whose dynamics depends on changes in the fluxes of specific ligands through the containment barriers that are the biological membranes. The regulation of this complex dynamic equilibrium is mainly due to the activity of border proteins, that must be able to interact simultaneously with the lipid bilayer and the extracellular milieu. Endocannabinoid receptors, that include type-1 and type-2 cannabinoid receptors, the transient vanilloid potential receptors and the peroxisome proliferator-activated receptors, represent one of the most intriguing examples of "border" proteins. They have also been identified as important drug discovery targets with potential therapeutic applications, from antiemesis, appetite enhancement, analgesia, glaucoma treatment, and immune suppression. However, as yet the molecular details of endocannabinoid receptor regulation remain elusive. In this review we summarize the most relevant aspects of the structural/functional characterization of these receptors, with a focus on the active role played by biological membranes (in particular lipid rafts) in the modulation of their accessibility and mode of ligand binding. Based on available evidence, we propose that endocannabinoid receptors can be regulated by the rate of interlayer exchange and lateral diffusion of endocannabinoid/cholesterol complexes within lipid bilayers, thus suggesting innovative approaches for the therapeutic exploitation of the membrane component of endocannabinoid signaling.

journal_name

Curr Med Chem

authors

Dainese E,Oddi S,Maccarrone M

doi

10.2174/092986710790980087

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

1487-99

issue

14

eissn

0929-8673

issn

1875-533X

pii

BSP/CMC/E-Pub/ 097

journal_volume

17

pub_type

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