The Role of Extracellular Calcium on Zinc Hydroxide-Induced Superoxide Production in Rat Neutｒophils

The purpose of this work was to study whether extracellular calcium concentration and voltage-gated calcium channels might influence zinc hydroxide-in-duced superoxide production in rat neutrophils. An increase in extracellular calcium concentration augmented superoxide production. Zinc hydroxide caused an elevation of intracellular free calcium concentration ([Ca2+]I) in parallel with extracellular calcium concentration. Four calcium channel antagonists were tested for their ability to inhibit superoxide production. The relative order of potency of antagonists was varapamil > diltiazem > nifedipine. Flunarizine was ineffective. The calmodulin antagonist (W-7)and the intracellar free calcium chalactor, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM), inhibited superoxide production. The inhibition of supperoxide production by a tyrosine kinase inhibitor, 4',5,7-trihydroxyisoflavone (genistein), was 50% of maximum. The results suggest that zinc hydroxide can stimulate superoxide production in neutrophils mainly by opening the voltage-gated calcium channels, facilitating the influx of extracellular calcium and an elevation of [Ca2+]I.

Zinc hydroxide

Superoxide

Neutｒophils

Zinc fume fever