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

1

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 P_2u purinoceptors, a subclass of P₂‐purinoceptors.

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 P_2u 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 P_2U‐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.

DOI: 10.1111/j.1476-5381.1995.tb16643.x

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