Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of β-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex

In this study, we investigated the effect of a 10-day treatment with high doses of morphine (10 mg/kg per day) on maj or components and functional state of the β-adrenergic receptor (β-AR) signaling system in the rat cerebral cortex. β-ARs were characterized by radioligand binding assays and amounts of various G protein subunits, adenylyl cyclase (AC) isoforms, G protein-coupled receptor kinases (GRKs), and β-a rrestin were examined by Western blot analysis. AC activity was determined as a measure of functionality of the signaling system. We also assessed the partitioning of selected signaling proteins between the lipid raft and non-raft fractions prepared from cerebrocortical plasma membranes. Morphine tr eatment resulted in a significant upregulation of β-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III). There was no change in quantity of G proteins and some other signaling molecules (AC-IV, AC-V/VI, GRK2, GRK5, GRK6, and β-arrestin) compared with controls. Interestingly, morphine exposure ca used a partial redistribution of β-ARs, Gsα, Goα, and GRK2 between lipid rafts and bulk plasma membranes. Spatial localization of other signaling molecules within the plasma membrane was not changed. Basal as well as fluoride- and forskolin-stimulated AC activities were not significantly different in membrane preparations from control and morph ine-treated animals. However, AC activity stimulated by the beta-AR agonist isoprenaline was markedly increased. This is the fir...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research