Endoplasmic reticulum (ER) and lysosomes are physiologically active, physically and functionally connected intracellular Ca2+ stores. In this study we investigated agonist-triggered Ca2+ release from these two stores in mouse microvascular endothelial bEND.3 cells. Addition of nigericin to discharge lysosomal Ca2+ did not affect endoplasmic reticulum Ca2+ release induced by cyclopiazonic acid (CPA) and vice versa, suggesting lysosomes and ER were separate Ca2+ stores whose Ca2+ content was not readily reduced by depletion of the counterpart. ATP triggered Ca2+ release was partially inhibited by Ned-19 (lysosomal two-pore channel inhibitor) or xestospongin C (inositol 1,4,5-trisphosphate receptor-channel inhibitor), suggesting ATP mobilized Ca2+ from both ER and lysosomes. Whilst ATP-triggered Ca2+ release did not affect subsequent CPA- or nigericin-induced Ca2+ discharge, pretreatment with either CPA or nigericin abolished subsequent ATP-triggered Ca2+ release. Thus, the empty state of ER suppressed lysosomal Ca2+ release elicited by ATP, and vice versa, the empty state of lysosome inhibited ATP triggered Ca2+ release from ER. These data suggest cross-talk of the two organelles on the Ca2+ filling state to regulate agonist-stimulated Ca2+ release of each other.

• MeSH
• Adenosine Triphosphate metabolism   pharmacology   MeSH
• Cell Line MeSH
• Endoplasmic Reticulum * metabolism   drug effects   MeSH
• Endothelial Cells * metabolism   drug effects   MeSH
• Indoles pharmacology   MeSH
• Lysosomes * metabolism   drug effects   MeSH
• Mice MeSH
• Nigericin pharmacology   MeSH
• Calcium * metabolism   MeSH
• Calcium Signaling * drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adenosine Triphosphate MeSH
• cyclopiazonic acid MeSH Browser
• Indoles MeSH
• Nigericin MeSH
• Calcium * MeSH