Stimulation of dopamine receptors inhibited Ca2+-calmodulin-dependent protein kinase II activity in rat striatal slices.
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.
Hou
X Y
XY
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
Tang
F M
FM
Zhang
G Y
GY
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
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