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.