title: Modulation of early [Ca2+]i rise in metabolically inhibited endothelial cells by xestospongin C.
abstract: When energy metabolism is disrupted, endothelial cells lose Ca(2+) from endoplasmic reticulum (ER) and the cytosolic Ca(2+) concentration ([Ca(2+)](i)) increases. The importance of glycolytic energy production and the mechanism of Ca(2+) loss from the ER were analyzed. Endothelial cells from porcine aorta in culture and in situ were used as models. 2-Deoxy-D-glucose (2-DG, 10 mM), an inhibitor of glycolysis, caused an increase in [Ca(2+)](i) (measured with fura 2) within 1 min when total cellular ATP contents were not yet affected. Stimulation of oxidative energy production with pyruvate (5 mM) did not attenuate this 2-DG-induced rise of [Ca(2+)](i), while this maneuver preserved cellular ATP contents. The inhibitor of ER-Ca(2+)-ATPase, thapsigargin (10 nM), augmented the 2-DG-induced rise of [Ca(2+)](i). Xestospongin C (3 microM), an inhibitor of D-myo-inositol 3-phosphate [Ins(3)P]-sensitive ER-Ca(2+) release, abolished the rise. The results demonstrate that the ER of endothelial cells is very sensitive to glycolytic metabolic inhibition. When this occurs, the ER Ca(2+) store is discharged by opening of the Ins(3)P-sensitive release channel. Xestospongin C can effectively suppress the early [Ca(2+)](i) rise in metabolically inhibited endothelial cells.
authors.affiliation: Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany. Matthias.Schaefer@physiologie.med.uni-giessen.de
authors.forename: M
authors.initials: M
authors.lastname: Schäfer
authors.forename: D
authors.initials: D
authors.lastname: Bahde
authors.forename: B
authors.initials: B
authors.lastname: Bosche
authors.forename: Y
authors.initials: Y
authors.lastname: Ladilov
authors.forename: C
authors.initials: C
authors.lastname: Schäfer
authors.forename: H M
authors.initials: HM
authors.lastname: Piper
authors.forename: T
authors.initials: T
authors.lastname: Noll
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D047028:Macrocyclic Compounds; D010080:Oxazoles / Q000494:pharmacology*; D012966:Sodium Cyanide / Q000494:pharmacology; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D047028:Macrocyclic Compounds; D010080:Oxazoles; C108644:xestospongin A; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000252:Calcium-Transporting ATPases; D012966:Sodium Cyanide; D002118:Calcium