Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells

Schuichi Koizumi, Makoto Ikeda, Kaori Inoue, Ken Nakazawa, Kazuhide Inoue

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 μM ATP in a concentration-dependent manner over a concentration range from 3 to 300 μM. High concentration of Zn2+ (>1 mM) inhibited the release. Zn2+ (10 μM) 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 μM), whereas high concentration of Zn2+ (>300 μM) attenuated the response. The dopamine release evoked by 30 μM ATP in the presence of 10 μM Zn2+ were suppressed by suramin (30 μM), an antagonist to P2-purinoceptors, to an extent similar to that in the absence of Zn2+. Zn2+ (1-100 μM) 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 Ca2+-depletion. Under whole-cell voltage-clamp, Zn2+ (10 μM) augmented by two-fold the peak amplitude of an inward current evoked by 30 μM 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 Ca2+-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.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalBrain Research
Volume673
Issue number1
DOIs
Publication statusPublished - Feb 27 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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