Opioid-Receptor (OR) Signaling Cascades in Rat Cerebral Cortex and Model Cell Lines: the Role of Plasma Membrane Structure
Abstract
Proteomic analysis of plasma membrane fractions (PM) izolated from brain cortex of rats exposed to increasing doses of morphine (10-50 mg/kg) for 10 days indicated that the brain cortex of morphine-treated animals can not be regarded as being adapted to this drug as significant up-regulation of proteins functionally related to oxidative stress and alternation of brain energy metabolism occurred. The number of delta-OR was increased 2x and their sensitivity to monovalent cations altered.
Our studies of plasma membrane structure and function in context with desensitization of GPCR action were extended by data indicating participation of cholesterol-enriched membrane domains in agonist-specific internalization of delta-OR. In HEK293 cells stably expressing delta-OR-Gi1alfa fusion protein, depletion of PM cholesterol was associated with decrease (by two-orders of magnitude) in affinity /potency of G-protein-response to agonist stimulation; maximum response was unchanged.
Hydrophobic interior of isolated PM became more "fluid", chaotically organized and more accessible to water molecules.