ATP enhances catecholamine uptake into PC12 cells.
Catecholamine uptake into PC12 cells, in the presence and absence of ATP, was measured in a bicarbonate-buffered Krebs Ringer. ATP enhanced significantly the uptake in a dose-dependent manner with maximal uptake at 1-3 mM. ATP increased the Vmax of uptake by 3-5 fold for both dopamine 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 uptake was not observed with metabolites of ATP. GTP and UTP were equally effective 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 that ATP is an allosteric modulator of the transporter and that a stable ATP analog, with ATP-like enhancement of dopamine uptake, may be an effective cocaine antagonist.
Eshleman
A
A
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA.
Dunigan
C
C
Shamoo
A
A
Eldefrawi
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D001639:Bicarbonates; D000255:Adenosine Triphosphate; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine