title: Protein kinase G regulates β-synuclein in response to repeated exposure to cocaine in the rat dorsal striatum in a Ca²⁺-dependent manner.
abstract: Protein kinase G (PKG) activation plays a crucial role in neuronal plasticity after repeated exposure to cocaine in the dorsal striatum. The present study investigated the characteristics of β-synuclein expression by PKG activation after repeated cocaine administration in the rat dorsal striatum. The results demonstrated that repeated, but not acute, exposure to cocaine (20mg/kg) once a day for 7 consecutive days significantly upregulated expression of β-synuclein. Furthermore, this upregulation was decreased by the depletion of Ca(2+), but not blockade of Na(+) influx. Blockade of N-methyl-d-aspartate (NMDA) receptors and ryanodine-sensitive Ca(2+) channels also decreased the elevation of β-synuclein expression by repeated cocaine administration. Inhibition of neuronal nitric oxide synthase, which can activate PKG, did not alter the expression of β-synuclein elevated by repeated cocaine administration. These findings suggest that the expression of β-synuclein can be regulated by Ca(2+)-dependent PKG activation via stimulation of NMDA receptors and voltage-operated Ca(2+) channels in the endoplasmic reticulum in the dorsal striatum.
authors.affiliation: Department of Biological Sciences, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 609-735, Republic of Korea.
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 609-735, Republic of Korea. Electronic address: eschoe@pusan.ac.kr.
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D051846:beta-Synuclein / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D051846:beta-Synuclein; D052248:Nitric Oxide Synthase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D003042:Cocaine; D002118:Calcium
keywords: Calcium channel; Drug addiction; Glutamate receptor; Protein kinase; Synuclein