Morphine Binds Creatine Kinase B and Inhibits Its Activity

• Published in: Frontiers in cellular neuroscience Vol. 12; p. 464
• Main Authors: Weinsanto, Ivan, Mouheiche, Jinane, Laux-Biehlmann, Alexis, Delalande, François, Marquette, Arnaud, Chavant, Virginie, Gabel, Florian, Cianferani, Sarah, Charlet, Alexandre, Parat, Marie-Odile, Goumon, Yannick
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 03.12.2018; Frontiers; Frontiers Media S.A
• Subjects: Analgesics; Animals; Binding sites; Brain; complex; Creatine; Creatine kinase; Detergents; Dopamine; Energy metabolism; Enzymatic activity; Experiments; Gel electrophoresis; high affinity; Imidazoline; Kinases; Life Sciences; ligand-binding protein; Ligands; Mammals; Metabolism; Morphine; Neurobiology; Neurons and Cognition; Neuroscience; Pain; Proteins; Reducing agents; Sodium lauryl sulfate; France; Germany; high affinity; ligand-binding protein; creatine kinase; complex; morphine
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2018.00464

Morphine is an analgesic alkaloid used to relieve severe pain, and irreversible binding of morphine to specific unknown proteins has been previously observed. In the brain, changes in the expression of energy metabolism enzymes contribute to behavioral abnormalities during chronic morphine treatment. Creatine kinase B (CK-B) is a key enzyme involved in brain energy metabolism. CK-B also corresponds to the imidazoline-binding protein I which binds dopamine (a precursor of morphine biosynthesis) irreversibly. Using biochemical approaches, we show that recombinant mouse CK-B possesses a μM affinity for morphine and binds to morphine . The complex formed by CK-B and morphine is resistant to detergents, reducing agents, heat treatment and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). CK-B-derived peptides CK-B and CK-B were identified as two specific morphine binding-peptides. , morphine (1-100 μM) significantly reduces recombinant CK-B enzymatic activity. Accordingly, morphine administration (7.5 mg/kg, i.p.) to mice significantly decreased brain extract CK-B activity compared to saline-treated animals. Together, these results show that morphine strongly binds CK-B and inhibits its activity and .