ATP receptors in psychosis

The possible implication of P-2-receptors in psychosis was examined using r at pheochromocytoma PC12 cells as a model neuron. The effects of haloperido l and chlorpromazine, typical antipsychotic drugs, and fluspirilene and pim ozide, atypical antipsychotic drugs of diphenylbutylpiperidines (DPBPs), on ATP-evoked increase in intracellular Ca2+ concentration ([Ca]i) and dopami ne release were investigated using PC12 cells. Haloperidol and chlorpromazi ne significantly attenuated the rise in [Ca]i and dopamine release evoked b y 100 mu M ATP. Fluspirilene or pimozide attenuated the Ca2+ response to AT P, but they did not inhibit the release of dopamine evoked by ATP. The inhi bition by antipsychotic drugs on the ATP-evoked [Ca]i rise were not through the antagonism of dopamine D-2 or D-1 receptor because antagonist and agon ist of dopamine D-2-receptor as well as those of dopamine D-1-receptor had no effect on the ATP-evoked [Ca]i rise. In the meanwhile, the effects of fl uspirilene and pimozide on the rise in [Ca]i and dopamine release evoked by high concentration of KCl (high K) were the same as that of haloperidol an d chlorpromazine. All of these drugs inhibited high K-evoked responses simi larly. The results suggest that the mechanism of the action of fluspirilene and pimozide is very different from that of haloperidol and chlorpromazine on ATP-evoked dopamine release. This may be a clue for the explanation of the difference of clinical effects of these antipsychotics.