We previously demonstrated that 5-hydroxytryptamine (5-HT) enhances the cationic current activated by extracellular ATP in rat pheochromocytoma PC12 cells. We report here that pertussis toxin (PTX) modulates this 5-HT-dependent enhancement in these cells. 5-HT potentiated ATP-evoked intracellular Ca2+ concentration ([Ca]i) rise and dopamine release over a concentration range from 1 to 100 μM. When cells were pre-treated with PTX, this potentiation was accentuated. Pretreatment with PTX also accentuated the 5-HT dependent enhancement of the ATP-activated current. These results suggest that the enhancement by 5-HT of the ATP-evoked responses is negatively regulated by a mechanism mediated through PTX-sensitive GTP-binding protein.
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