title: Endothelin-1 suppresses plasma membrane Ca++-ATPase, concomitant with contraction of hepatic sinusoidal endothelial fenestrae.
abstract: Intracytoplasmic free calcium ions (Ca++) are maintained at a very low concentration in mammalian tissue by extruding Ca++ from the cytoplasm against a steep extracellular Ca++ concentration gradient, mainly through the activity of plasma membrane Ca++ pump-ATPase. The present study aimed to elucidate how endothelin-1 (ET-1) affects the morphology of sinusoidal endothelial fenestrae and ultrastructural distribution of plasma membrane ATPases and intracytoplasmic free Ca++ in isolated rat hepatic sinusoidal endothelial cells. Sinusoidal endothelial fenestrae were observed by scanning electron microscope. Ando's electron cytochemical method was used for ultrastructural localization of Ca++-Mg++-ATPase activity, electron immunogold postembedding method for Ca++ pump-ATPase immunoactivity, and antimonate method for intracytoplasmic free Ca++. Addition of ET-1 to sinusoidal endothelial cells significantly decreased Ca++-Mg++-ATPase activity and Ca++ pump-ATPase expression and increased intracytoplasmic free Ca++ concentration, concomitant with a decrease in diameter of sinusoidal endothelial fenestrae. Co-treatment with Bosentan abolished the actions of ET-1. These results suggest that ET-1 suppresses Ca++-Mg++-ATPase activity and Ca++ pump-ATPase expression on the plasma membrane of sinusoidal endothelial fenestrae, thereby attenuating the extrusion of intracytoplasmic free Ca++ into the extracellular space, leading to an increased concentration of intracytoplasmic free calcium ions and contraction of sinusoidal endothelial fenestrae.
authors.affiliation: Department of Internal Medicine and the Laboratory of Pathology, Kitasato Medical Center Hospital, Saitama. yokomori-hr@kitasato.or.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yokomori
authors.forename: Masaya
authors.initials: M
authors.lastname: Oda
authors.forename: Mariko
authors.initials: M
authors.lastname: Ogi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nomura
authors.forename: Kayo
authors.initials: K
authors.lastname: Fujimaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kamegaya
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tsukada
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D004727:Endothelium / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases