Accumulating evidence has indicated that membrane-permeable G protein-coupled receptor ligands can enhance cell surface targeting of their cognate wild-type and mutant receptors. This pharmacological chaperoning was thought to result from ligand-mediated stabilization of immature receptors in the endoplasmic reticulum (ER). In the present study, we directly tested this hypothesis using wild-typ...

Quaternary narcotic antagonists that are assumed not to penetrate the blood-brain barrier following systemic administration are commonly used to distinguish between peripheral and central actions of opiates. In mammals, these antagonists have a lower affinity for opioid receptors than their tertiary parent compounds. The relative affinity of quaternary vs. tertiary antagonists either for opioid...

The three opioid receptors (μ, δ, and κ) are important targets for pain management and have also shown promise as targets for treatment of addiction and mood disorders. In the past, research in the field commonly focused on analysis of structure-activity relationships (SAR) and ligands’ conformational preferences. Recently, advancements permitted determination of crystal structures for each of ...

BACKGROUND AND PURPOSE In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in δ-opioid receptor knockout mice (DOPr(-/-) ). Hence, we investigated δ-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on t...

Delta and mu opioid receptors (DORs and MORs) are inhibitory G protein-coupled receptors that reportedly cooperatively regulate the transmission of pain messages by substance P and TRPV1-expressing pain fibers. Using a DOReGFP reporter mouse we now show that the DOR and MOR are, in fact, expressed by different subsets of primary afferents. The MOR is expressed in peptidergic pain fibers, the DO...

Received: December 20, 2016 Revised: February 14, 2017 Accepted: February 17, 2017 Abstract: Background: Pruritus is a very disturbing secondary effect that appears after epidural or intrathecal administration of opioid drugs, especially in the management of postoperative pain. It is induced by the activation of mu opioid receptors and it can often be even more unpleasant than the pain being tr...

mu opioid receptors are targets of native opioid peptides and addictive analgesic drugs. A major clinical liability of opiate drugs is their ability to cause physiological tolerance. Individual opiates, such as morphine and etorphine, differ both in their ability to promote physiological tolerance and in their effects on receptor regulation by endocytosis. Here, we demonstrate that arrestins pl...