The H2O2‐Generating Enzyme, Xanthine Oxidase, Decreases Luminal Ca2+ Content of the IP3‐Sensitive Ca2+ Store in Vascular Endothelial Cells

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Abstract
Xanthine oxidase inhibits agonist-stimulated Ca2+ signaling in calf pulmonary artery endothelial cells by an H2O2-dependent mechanism. We investigated the effect of xanthine oxidase on luminal Ca2+ content of the inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ store. Luminal Ca2+ content was estimated from the net release of Ca2+ activated by 2,5-di-t-butylhydroquinone (BHQ), an inhibitor of microsomal Ca2+ pumps. Initially, xanthine oxidase depleted the IP3-sensitive Ca2+ store of releasable Ca2+, but with more prolonged incubation, the enzyme also depleted non-IP3-sensitive stores. In addition, xanthine oxidase inhibited capacitative Ca2+ influx. Similar results were observed when thapsigargin was substituted for BHQ. Depletion of luminal Ca2+ content within the IP3-sensitive Ca2+ store contributes to xanthine oxidase inhibition of Ca2+ signaling in vascular endothelial cells.