Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells.
The effects of zinc (Zn2+) on ATP-evoked dopamine release was investigated in rat pheochromocytoma PC12 cells. Zn2+ potentiated the dopamine release evoked by 30 microM ATP in a concentration-dependent manner over a concentration range from 3 to 300 microM. High concentration of Zn2+ (> 1 mM) inhibited the release. Zn2+ (10 microM) shifted the concentration-response curve of the ATP-evoked dopamine release to the left without affecting the maximal response. The dopamine release evoked by 40 mM KCl was not affected by Zn2+ (1-100 microM), whereas high concentration of Zn2+ ( > 300 microM) attenuated the response. The dopamine release evoked by 30 microM ATP in the presence of 10 microM Zn2+ were suppressed by suramin (30 microM), an antagonist to P2-purinoceptors, to an extent similar to that in the absence of Zn2+. Zn2+ (1-100 microM) enhanced the ATP-evoked increase in intracellular Ca2+ concentration ([Ca]i) in the cells. The Ca2+ responses to ATP in the presence and absence of Zn2+ were abolished by external Ca(2+)-depletion. Under whole-cell voltage-clamp, Zn2+ (10 microM) augmented by two-fold the peak amplitude of an inward current evoked by 30 microM ATP. Taken together, it is suggested that Zn2+ enhances the ATP-evoked dopamine release by increasing sensitivity to ATP. The enhancement may be due to the augmentation of ATP-gated Ca(2+)-influx, but not due to modulation of cellular machinery downstream to [Ca]i rise. The enhancement of the ATP-mediated responses may underlie modulation by Zn2+ of physiological functions in various types of neuronal cells.
Koizumi
S
S
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Ikeda
M
M
Inoue
K
K
Nakazawa
K
K
Inoue
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016716:PC12 Cells; D051381:Rats; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology*
D013498:Suramin; D000255:Adenosine Triphosphate; D015032:Zinc; D002118:Calcium; D004298:Dopamine