Mechanisms of interaction between adenosine receptor subtypes on hippocampal serotonin release]

To clarify the mechanisms of interaction between adenosine receptor subtypes (A1R and A2R) on 5-HT release, the present study determined the effects of adenosine receptor subtypes on voltage-sensitive Ca(2+)-channels (VSCCs), protein-kinases (PKs) and synaptic-proteins (SNAREs) related 5-HT release using microdialysis in freely moving rat. A1R-antagonists increased basal 5-HT release, which was reduced by inhibitors of N-VSCC, PKC and syntaxin predominantly, and by inhibitors of PKA and synaptobrevin weakly, but was not affected by P-VSCC inhibitor. In the presence of A1R-antagonist, A2R-agonists increased basal 5-HT release, whose action was inhibited by P-VSCC, PKA and synaptobrevin inhibitors predominantly and reduced by N-VSCC, PKC and syntaxin inhibitors weakly. Under the condition of adenylate-cyclase activation in the absence of A1R-antagonists, A2R-agonists increased basal 5-HT release. K(+)-evoked 5-HT release was enhanced by A1R-antagonist and A2R-agonist, whose actions were inhibited by P-VSCC, PKA and synaptobrevin inhibitors predominantly. These results suggest that an activation of A1R suppresses 5-HT release via an inhibition of N-VSCC/PKC/syntaxin and P-VSCC/PKA/synaptobrevin, and an activation of A2-R stimulates 5-HT release via an enhancement of P-VSCC/PKA/synaptobrevin. Therefore PKA activity plays an important role in the interaction between A1R and A2R on hippocampal 5-HT release.