Continuously infusing quinpirole decreases Ca2+/calmodulin-dependent phosphorylation in mouse striatum.
Continuously administering the D2 dopamine agonist quinpirole to mice for 6 days produces an initial stereotypy that is reduced by 2 h and is absent from 3 h to the 6 day duration of the infusion. In an attempt to determine the biochemical correlates for this down-regulation of stereotypic behavior, the effects of continuously administering quinpirole on a number of biochemical parameters were measured in mouse corpus striatum. After 6 days of infusion with quinpirole, the striata were analyzed for D1 and D2 dopamine receptors, for the activities of several protein phosphorylation reactions which are thought to be involved in receptor activity and for the levels of calmodulin-binding proteins. Quinpirole decreased the D2 receptors in striatum and produced a small but statistically non-significant increase in D1 receptors, resulting in a significant increase in the ratio of D1 to D2 dopamine receptors. An examination of the effects of quinpirole on protein phosphorylation systems showed that the agonist failed to alter the activity of cyclic AMP-dependent protein kinase or protein kinase C but significantly decreased the Ca2+/calmodulin-dependent phosphorylation of striatal membranes. However, this decrease in Ca2+/calmodulin-dependent phosphorylation was not associated with changes in the levels of calmodulin-binding proteins. The results suggest that behavioral down-regulation following the continuous administration of a D2 dopamine agonist is associated with at least two biochemical events: a down-regulation of D2 dopamine receptors and a decrease of Ca2+/calmodulin-dependent phosphorylation of striatal membranes.
Zhang
S P
SP
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia 19129.
Zhou
L W
LW
Natsukari
N
N
Weiss
B
B
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019257:Quinpirole; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D004873:Ergolines; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D004533:Egtazic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium