The H2O2-generating enzyme, xanthine oxidase, decreases luminal Ca2+ content of the IP3-sensitive Ca2+ store in vascular endothelial cells.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Depletion of luminal Ca2+ content within the IP3-sensitive Ca2+ store contributes to xanthine oxidase inhibition of Ca2+ signaling in vascular endothelial cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006873:Hydroquinones / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D017382:Reactive Oxygen Species; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D013729:Terpenes; C019359:2,5-di-tert-butylhydroquinone; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D002118:Calcium