Dopamine-glutamate interaction in rat striatal slices: changes of CCDPK II, PKA, and LDH activity by receptor-mediated mechanisms.

AIM

To study the effects of dopamine (DA) and glutamate (Glu) and their receptor agonists/antagonists on Ca2+/calmodulin-dependent protein kinase II (CCDPK II), cyclic AMP-dependent protein kinase A (PKA) activities and the LDH release in rat striatal slices, and to examine the interaction between DA and Glu transmitter systems in striatum.

METHODS

The activities of CCDPK II, PKA, and the release of LDH were determined with the 32P-incorporation and colorimetry respectively in rat striatal slices.

RESULTS

(1) Exogenous DA, D1 receptor agonist SKF 38393 and D2 receptor agonist LY 171555 reduced CCDPK II activity in striatal slices; Glu also inhibited CCPPK II activity in a concentration-dependent manner. NMDA receptor antagonist MK-801 could antagonize the inhibitory effect of SKF 38393 and LY 171555 on the CCDPK II activity. D1 and D2 receptor antagonists SCH 23390 and spiperone could also antagonize the decrease of CCDPK II activity induced by Glu; (2) DA and SKF 38393 markedly increased PKA activity in striatal slices, which was reduced by MK-801; (3) DA and Glu increased the release of LDH from the striatal neurons in a concentration-dependent manner. MK-801 antagonized the increase of LDH induced by DA. Spiperone, rather than SCH 23390, could reduce the release of LDH from striatal neuron in the presence of Glu.

CONCLUSION

The interaction between DA and Glu transmitter systems is found in the regulation of the CCDPK II and PKA activities and cell function in the striatum.