Arachidonic acid inhibits norepinephrine release through blocking of voltage‐sensitive Ca²⁺ channels in PC12 cells

Abstract

We studied the mechanism of arachidonic acid on the secretion of a neurotransmitter in rat pheochromocytoma PC12 cells. Arachidonic acid inhibited the 70 mM K⁺‐induced secretion of norepinephrine. Arachidonic acid also inhibited the 70 mM K⁺‐induced Ca²⁺ mobilization which is due to the opening of the voltage‐sensitive Ca²⁺ channels (VSCC). Both the half maximal inhibitory concentration (IC₅₀) of the norepinephrine secretion and VSCC coincided at 30 μM. The major oxidized metabolites of arachidonic acid, prostaglandins did not mimic the inhibitory effect of arachidonic acid. Nordihydroguaiaretic acid (NDGA) and indomethacin which are inhibitors of lipoxygenase and cyclooxygenase, respectively, did not block the inhibitory effect of arachidonic acid. The results suggest that arachidonic acid serves as a signal itself, not in the form of metabolites. The pretreatment of various K⁺ channel blockers such as 4‐aminopyridine, tetraethylammonium, glipizide, or glibenclamide also did not show any effect on the inhibitory effect of arachidonic acid. Through these results we suggest that arachidonic acid regulates VSCC directly and affects the secretion of neurotransmitters.

Key words:

• Arachidonic acid
• Cytosolic Ca²⁺
• Neurotransmitter secretion
• Voltage‐sensitive Ca²⁺ channels
• PC12 cells

Notes

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