title: Nicorandil inhibits the release of TNFalpha from a lymphocyte cell line and peripheral blood lymphocytes.
abstract: Modulation of cytokine release may be of interest in modulating inflammatory diseases. This study determined whether nicorandil, a potassium channel opener, and nitric oxide (NO) donor could inhibit the release of tumour necrosis factor alpha (TNFalpha) from lymphocytes. Nicorandil significantly and dose-dependently inhibited the TNFalpha release from a human Epstein Barr virus-transformed B lymphocyte cell line (EBV-B) and peripheral blood B and T lymphocytes. The inhibition was reversed by the addition of both potassium channel inhibitor glibenclamide and the guanylyl cyclase inhibitor 1H-(1,2,4) oxadiazolo (4,3) quinoxalin-1-one (ODQ). Other potassium channel openers, pinacidil, or the nicorandil analogue SG-209, however, failed to demonstrate inhibition of TNFalpha release. The NO scavenger haemoglobin was unable to reverse the nicorandil-induced TNFalpha inhibition, but in contrast to this, sodium nitroprusside (SNP) partially inhibited the release, which was reversed by haemoglobin. Nicorandil is able to inhibit TNFalpha release from lymphocytes, which requires the dual modes of both potassium channel opening and the nitrate moiety. Moreover, NO donation mechanism appears to be more dominant in the nicorandil inhibitory activity in lymphocytes.The dual mechanism involved in the inhibition of this cytokines may represent a novel therapeutical approach in the modulation of inflammatory disease.
authors.affiliation: Inflammation Research Unit, School of Pathology, Faculty of Medicine, UNSW and Department of Respiratory Medicine, Prince of Wales Hospital, NSW 2031, Randwick, Australia.
authors.forename: X M
authors.initials: XM
authors.lastname: Wei
authors.forename: G J
authors.initials: GJ
authors.lastname: Heywood
authors.forename: N
authors.initials: N
authors.lastname: Di Girolamo
authors.forename: P S
authors.initials: PS
authors.lastname: Thomas
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D005905:Glyburide / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000254:growth & development; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D009536:Niacinamide; D020108:Nicorandil; D019323:omega-N-Methylarginine; D020110:Pinacidil; C035663:SG 209; D019001:Nitric Oxide Synthase; D013755:Tetradecanoylphorbol Acetate; D005905:Glyburide