title: LP-805, a releaser of endothelium-derived nitric oxide, activates an endothelial calcium permeable non-specific cation channel.
abstract: The actions of LP-805, a releaser of endothelium-derived nitric oxide, on Ca2+ permeable non-specific cation channel in cultured bovine pulmonary artery endothelial cells (BPAECs) were investigated using patch-clamp technique. In Ca2+ saline bath solution, 10 microM LP-805 increased inward and outward currents. LP-805 evoked currents were reversibly blocked by 50 microM La3+, an inorganic Ca2+ influx blocker. In Ca2+ and Na+ free saline bath solution, 10 microM LP-805 did not evoke these currents, when 2 mM Ca2+ was then added to the bath the inward current increased. Furthermore, in the Na+ saline bath solution (Ca2+ free), 10 microM LP-805 increased similar inward and outward currents, which were blocked by 50 microM La3+. LP-805 evoked currents were carried by either Ca2+ or Na+. With the pipette solution containing 11 mM EGTA, 10 microM LP-805 activated the inward and outward currents. The increase of inward and outward currents by 10 microM LP-805 was inhibited by 1 mM Ni2+ but not by 1 microM nicardipine or 50 microM SKF 96365. In conclusion, LP-805 increases Ca2+ influx into vascular endothelial cells through Ca2+ permeable non-specific cation channels. This may explain the release of endothelium-derived nitric oxide in endothelial cells by LP-805.
authors.affiliation: Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Inazu
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: E E
authors.initials: EE
authors.lastname: Daniel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D011720:Pyrazoles; D011743:Pyrimidines; D014665:Vasodilator Agents; C073993:8-tert-butyl-6,7-dihydropyrrolo(3,2-e)-5-methylpyrazolo(1,5-a)pyrimidine-3-carbonitrile; D009569:Nitric Oxide; D002118:Calcium