ATP ENHANCES CATECHOLAMINE UPTAKE INTO PC12 CELLS

Catecholamine uptake into PC12 dells, in the presence and absence of A TP, was measured in a bicarbonate-buffered Krebs Ringer. ATP enhanced significantly the uptake in a dose-dependent manner with maximal uptak e at 1-3 mM. ATP increased the Vmax of uptake by 3-5 fold for both dop amine and norepinephrine, without a significant change in the Km. ATP- stimulated amine uptake was temperature- and Na+- dependent and robust in bicarbonate, but not in HEPES buffer. The ability to enhance uptak e was not observed with metabolites of ATP. GTP and UTP were equally e ffective to ATP in enhancing CA uptake. This uptake was less sensitive to uptake inhibitors in bicarbonate buffered media than in phosphate- buffered media, and more so in the presence of ATP. It is suggested th at ATP is an allosteric modulator of the transporter and that a stable ATP analog, with ATP-like enhancement of dopamine uptake, may be an e ffective cocaine antagonist.