Inhibition by Zn2+ of uridine 5‘ triphosphate‐induced Ca2+‐influx but not Ca2+‐mobilization in rat phaeochromocytoma cells

Schuichi Koizumi, Ken Nakazawa, Zazuhide Inoue

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32 Citations (Scopus)

Abstract

Uridine 5′‐triphosphate (UTP)‐evoked increase in intracellular Ca2+ concentration ([Ca]i) and release of dopamine were investigated in rat phaeochromocytoma PC12 cells. UTP (1–100 μm) evoked an increase in [Ca]i in a concentration‐dependent manner. This response was decreased to about 30% by extracellular Ca2+‐depletion, but not abolished. This [Ca]i rise was mimicked by 100 μ ATP but not by 100 μm 2‐methyl‐thio‐ATP or α, β‐methylene‐ATP in the absence of external Ca2+, suggesting that the response was mediated by P2u purinoceptors, a subclass of P2‐purinoceptors. The UTP‐evoked [Ca]i rise consisted of two components; a transient and a sustained one. When external Ca2+ was removed, the sustained component was abolished while the transient component was decreased by about 70% but did not disappear. These results suggest that UTP induces Ca2+‐obilization and, subsequently, Ca2+‐influx. The UTP‐evoked increase in [Ca]i was not affected by Cd2+ (100 and 300 μm) or nicardipine (30 μm), inhibitors of voltage‐gated calcium channels, but was significantly inhibited by Zn2+ (10–300 μm) in the presence of external Ca2+. Zn2+, however, did not affect the Ca2+ response to UTP in the absence of external Ca2+. UTP (30 μm‐1 mM) evoked the release of dopamine from the cells in a concentration‐dependent manner. This dopamine release was abolished by Ca2+‐depletion or Zn2+ but not by Cd2+ or nicardipine. Taken together, the data demonstrate that UTP stimulates P2U‐purinoceptors and induces a rise in [Cal both by Ca2+‐mobilization and Ca2+‐influx in PC12 cells. The dopamine release evoked by UTP requires external Ca2+ which may enter the cells through pathways sensitive to Zn2+ but insensitive to Cd2+ or nicardipine. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)1502-1508
Number of pages7
JournalBritish Journal of Pharmacology
Volume115
Issue number8
DOIs
Publication statusPublished - Aug 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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