title: Stimulation of dopamine receptors inhibited Ca2+-calmodulin-dependent protein kinase II activity in rat striatal slices.
abstract: OBJECTIVE
  To investigate the mechanism underlying dopaminergic neurotoxicity in the striatum during anoxia.
  
  
  METHODS
  Using rat striatal slices as an in vitro model, the activity of Ca2+-calmodulin-dependent protein kinase II (CCDPKII) was examined by the method of substrate phosphorylation 32P-incorporation.
  
  
  RESULTS
  Anoxia for 30 min greatly reduced CCDPKII activity by about 75 %. Reserpinization by repeated reserpine administration (1 mg . kg-1 . d-1 for 7 d, sc) preserved CCDPK II activity against the anoxia-induced decrease (about 40 % of control). The activity of CCDPKII was reduced significantly by exposure of rat striatal slices to micromolar concentrations of dopamine in the presence of extracellular Ca2+. Omission of Ca2+ in the incubation medium (with addition of 1 mmol/L egtazic acid) diminished the dopamine-induced decrease of the kinase activity. Application of apomorphine, a non-selective dopamine receptor agonist, produced a similar concentration-related decrease of CCDPKII activity. Exposure to SKF38393 (selective D1-like receptor agonist) or quinpirole (selective D2-like receptor agonist) also inhibited the kinase activity. The dopamine-induced decrease of CCDPKII activity was attenuated by preincubation with Sch-23390 (selective D1-like receptor antagonist) or domperidone (selective D2-like receptor antagonist).
  
  
  CONCLUSIONS
  Dopamine is involved in the anoxia-induced inhibition of CCDPKII activity by activation of both D1-like and D2-like receptors and influx of Ca2+, which may contribute to dopamine-mediated striatal neuronal damage.
authors.affiliation: Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Hou
authors.forename: F M
authors.initials: FM
authors.lastname: Tang
authors.forename: G Y
authors.initials: GY
authors.lastname: Zhang
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012110:Reserpine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D004298:Dopamine