In vivo trafficking of endogenous opioid receptors

Abstract

Several approaches have been taken for these in vivo studies. In many studies, the use of semiquantitative immuno-electron microscopy is the approach of choice. Endogenous opioid receptors display differential subcellular distributions with µ opioid receptor (MOPR) being mostly present on the plasma membrane and δ-and κ-opioid receptors (DOPR and KOPR, respectively) having a significant intracellular pool. Etorphine and DAMGO cause endocytosis of the MOPR, but morphine does not, except in some dendrites. Interestingly, chronic inflammatory pain and morphine treatment promote trafficking of intracellular DOPR to the cell surface which may account for the enhanced antinociceptive effects of DOPR agonists. KOPR has been reported to be associated with secretory vesicles in the posterior pituitary and translocated to the cell surface upon salt loading along with the release of vasopressin. The study of endogenous opioid receptors using in vivo models has produced some interesting results that could not have been anticipated in vitro. In vivo studies, therefore, are essential to provide insight into the mechanisms underlying opioid receptor regulation.

Sensory Neuron-Specific Mas-Related Gene-X1 Receptors Resist Agonist-Promoted Endocytosis

“…Absence of ␤ 3 -AR desensitization, first found in recombinant expression systems (Nantel et al, 1993), was confirmed in an endogenous cell system (Jockers et al, 1998). Similar findings were reported for the -opioid (Wang et al, 2008) and the somatostatin-4 receptor (Schreff et al, 2000), indicating that lack of receptor endocytosis is not an artifact per se because of heterologous protein expression.…”

Nicotine withdrawal and κ-opioid receptors

“…Desensitized and internalized KOPrs are expected to either resensitize and recycle back to the surface membrane, or be sorted to degradation pathways leading to downregulation (Wang et al 2008 and references there in). In neurons, the majority of KOPrs is located in the cytosol and this receptor pool might influence KOPr trafficking by facilitating the insertion of new receptors into the cell surface membrane (Svingos and Colago 2002;Wang et al 2008 and discussion there in). Hence, it is theoretically possible that prolonged agonist administration in vivo not to down-regulate KOPrs, since degraded receptors could be continuously replaced from a compensatorily maintained intracellular receptor pool.…”

Desensitization of δ-opioid receptors in nucleus accumbens during nicotine withdrawal

“…Thus, despite the DOPr desensitization in NAc shell and core, no receptor downregulation was evident. Little is known about the trafficking of DOPrs in vivo (Wang et al 2008 and references therein). It has been suggested that DOPrs are slowly recycled/ degraded after agonist-induced internalization in vivo (Pradhan et al 2009), and there is evidence in vitro that the post-endocytotic fate of the receptors is influenced by the type of agonist with the natural enkephalins promoting recycling and resensitization of receptor (Lecoq et al 2004).…”

“…Perhaps, receptor externalization is the preferable route following long-term pharmacological manipulation of the endogenous ligand in vivo. In striatal neurons, the majority of DOPrs is located in the cytosol (Wang and Pickel 2001;Wang et al 2008 and discussion therein), and a compensatorily maintained intracellular receptor pool during prolonged agonist exposure might influence DOPr trafficking by facilitating the insertion of new receptors into the cell surface membrane. The observation that the receptor mRNA in NAc shell tended to rise over the time indicates that compensatory receptor protein synthesis may occur in order to maintain receptor number.…”