Crosstalk between cdk5 and MEK–ERK signalling upon opioid receptor stimulation leads to upregulation of activator p25 and MEK1 inhibition in rat brain

• Published in: Neuroscience Vol. 215; pp. 17 - 30
• Main Authors: Ramos-Miguel, A, García-Sevilla, J.A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 26.07.2012; Elsevier
• Subjects: Analysis of Variance; Animals; Benzamides - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; cdk5; Cyclin-Dependent Kinase 5 - metabolism; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Fentanyl - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Male; MAP Kinase Kinase 1 - metabolism; MDL28170; MEK–ERK; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Narcotics - pharmacology; Neurology; opioid receptors; p25/p35; Phosphorylation - drug effects; Phosphorylation - physiology; Phosphotransferases - metabolism; Piperazines - pharmacology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Opioid - metabolism; SL327; Time Factors; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; PP-1; extracellular signal-regulated kinase; DMSO; JNK; N-methyl- d-aspartate; SL327; subcutaneous; cyclic AMP; BCA; MDL28170; corpus striatum; ctx; PKA; s.c; dopamine- and cAMP-regulated phosphoprotein of 32 kDa; i.p; enhanced chemiluminescence; phosphorylated; MAPK; SDS–PAGE; spontaneous withdrawal; str; MEK; dodecyl sulphate polyacrylamide gel electrophoresis; poly(ADP-ribose)-polymerase-1; SEM; cyclin-dependent kinase 5; MAPK phosphatase-1; standard error of the mean; c-Jun NH 2-terminal kinase or stress-activated protein kinase (SAPK); ERK; opioid receptors; DARPP-32; PARP; MEK–ERK; truncated DARPP-32; cAMP; ERK kinase; protein phosphatase-1; mitogen-activated protein kinase; bicinchoninic acid; dimethyl sulphoxide; NMDA; protein kinase A; phosphatase of activated cells; intraperitoneal; SW; cdk5; t-DARPP; ECL; p; cerebral cortex; PAC; MKP-1; p25/p35; Extracellular signal-regulated protein kinase; Rat; Enzyme; Transferases; Opioid receptor; Rodentia; Central nervous system; MEK-RK; Mitogen-activated protein kinase; Stimulation; Encephalon; Vertebrata; Mammalia; Animal
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2012.04.035

Graphical abstract Functional interactions between cdk5/p35/p25, neurotoxic/apoptotic signalling, DARPP-32/truncated (t)-DARPP, and MEK–ERK pathways upon the acute stimulation of opioid receptors in the rat corpus striatum. Highlights ► Acute/chronic opioid receptor stimulation upregulates cdk5 activator p25 in rat brain. ► p25 upregulation is dependent on MEK–ERK and calpain activity. ► Opiate agonists induce p-Thr75 DARPP-32, resulting in PKA inhibition. ► Opiate agonists induce p-Thr286 MEK1, resulting in MEK–ERK inhibition. ► cdk5/ERK crosstalk is important in opiate-induced neuroplasticity.