title: The cytosolic calcium concentration is affected by S-nitrosocysteine in human lymphomonocytes.
abstract: The homeostasis of cytosolic calcium [Ca2+](c) in mammalian cells is a complex phenomenon, requiring the contribution of many cellular and extracellular systems. Nitric oxide (NO) acts on [Ca2+](c), although the mechanism of this action is unknown. We study the release and the uptake of Ca2+ in the endoplasmic reticulum and its capacitative entry in human lymphomonocytes in the presence of the NO donor S-nitrosocysteine (CysNO) at low (16 microM) and at high (160 microM) concentrations by measuring the [Ca2+](c) by the Fura 2-AM method. Thapsigargin (TG), which inhibits sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), and nifedipine (NIF), which blocks the Ca2+ release from intracellular stores, are used to clarify the effects of NO on calcium movements. In the absence of extracellular Ca2+, CysNO decreases basal [Ca2+](c), whereas TG increases it as the result of SERCA inhibition. This effect of TG diminishes in the presence of the NO donor. In the presence of extracellular Ca2+(capacitative entry conditions), CysNO does not influence Ca2+ entry but reduces the toxic effects of TG connected to the increase of [Ca2+](c) in these conditions. The effect of NIF is, up to a certain extent, similar to that of CysNO, although the mechanisms of action of the two agents do not seem related. We conclude that CysNO participates in [Ca2+](c) homeostasis by stimulating the movement of the ion from the cytosol to other compartments.
authors.affiliation: Department of Internal Medicine, The Medical School, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. crlpal@unipg.it
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Palmerini
authors.forename: Michela
authors.initials: M
authors.lastname: Mazzoni
authors.forename: Carla
authors.initials: C
authors.lastname: Saccardi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arienti
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D026403:S-Nitrosothiols / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D026403:S-Nitrosothiols; D019284:Thapsigargin; C021315:S-nitrosocysteine; D009543:Nifedipine; D003545:Cysteine; D002118:Calcium