Pharmacological discrimination of protein kinase associated exocytosis mechanisms between dopamine and 3,4-dihydroxyphenylalanine in rat striatum using in vivo microdialysis.
To explore the exocytosis mechanism of dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of protein-kinase, cyclic-AMP-dependent protein-kinase (PKA), Ca(2+)-phospholipid-dependent protein-kinase (PKC) and Ca(2+)-calmodulin-dependent protein-kinase II (CaMK-II) on dopamine and DOPA releases in rat striatum using microdialysis. Basal DOPA and dopamine releases were reduced by PKC and CaMK-II inhibitors predominantly, and PKA inhibitor weakly. Ca(2+)-evoked releases were reduced by PKC and CaMK-II inhibitors, but not by PKA inhibitor. K(+)-evoked (20 min) releases were reduced by PKA and CaMK-II inhibitors predominantly, and PKC inhibitor weakly. Sustained K(+)-evoked (120 min) releases of DOPA and dopamine were reduced by CaMK-II inhibitor, but not by PKC or PKA. DOPA accumulation was reduced by PKA and CaMK-II inhibitors strongly, and PKC inhibitor weakly. Therefore, the present study demonstrates that striatal DOPA exocytosis is regulated by a similar protein kinase-associated exocytosis mechanism as that of dopamine.
Zhu
Gang
G
Department of Neuropsychiatry, School of Medicine, Hirosaki University, Hirosaki 036-8562, Japan.
Okada
Motohiro
M
Yoshida
Shukuko
S
Hirose
Shinichi
S
Kaneko
Sunao
S
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D004295:Dihydroxyphenylalanine; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D011188:Potassium; D004298:Dopamine