Mechanism of μ-Opioid Receptor-Magnesium Interaction and Positive Allosteric Modulation.

ABSTRACT: In the era of opioid abuse epidemics, there is an increased demand for understanding how opioid receptors can be allosterically modulated to guide the development of more effective and safer opioid therapies. Among the modulators of the μ-opioid (MOP) receptor, which is the pharmacological target for the majority of clinically used opioid drugs, are monovalent and divalent cations. Specifically, the monovalent sodium cation (Na⁺) has been known for decades to affect MOP receptor signaling by reducing agonist binding, whereas the divalent magnesium cation (Mg²⁺) has been shown to have the opposite effect, notwithstanding the presence of sodium chloride. Although ultra-high-resolution opioid receptor crystal structures have revealed a specific Na⁺ binding sit

SUBMITTER: Hu X 

PROVIDER: S-EPMC7036724 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature