title: Nitric oxide inhibits ATP-dependent Ca2+ uptake into platelet membrane vesicles.
abstract: The reduction by nitric oxide donors of Ca2+ mobilization in stimulated platelets lead us to investigate the direct effect of authentic NO on ATP-dependent Ca2+ uptake into platelet membrane vesicles. The effects of NO were compared to those of thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone, two specific inhibitors of the sarco/endoplasmic reticulum Ca2+-ATPases. All three compounds modulated the initial rate of ATP-dependent Ca2+ uptake. NO effects on the initial rate of active Ca2+ uptake were biphasic, with an inhibition above 10 nmol/L and a stimulation below this concentration. These effects could not be attributed to cGMP, its usual effector molecule, or to nitrite ions, its metabolic product. NO inhibitory effects were decreased after a five min incubation, indicating that they were due to a short-lived compound and reversible. These results suggest that NO is functionally coupled to SERCA pumps of the dense tubular system through a cGMP-independent mechanism.
authors.affiliation: Department of Pharmacology, CNRS URA 1482, René Descartes University, Necker Medical School, Paris, France.
authors.forename: M G
authors.initials: MG
authors.lastname: Pernollet
authors.forename: F
authors.initials: F
authors.lastname: Lantoine
authors.forename: M A
authors.initials: MA
authors.lastname: Devynck
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D006152:Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D009573:Nitrites; D013729:Terpenes; D009569:Nitric Oxide; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; D002118:Calcium