title: Ibudilast, an anti-allergic and cerebral vasodilator, modulates superoxide production in human neutrophils.
abstract: We evaluated the effect of ibudilast on superoxide generation in human neutrophils by chemiluminescence development using luciferine analog, FCLA. By incubating neutrophils with ibudilast (2-200 microM) for more than 10 minutes, fMLP- or PMA-induced chemiluminescence was enhanced. However, the fMLP-induced chemiluminescence was suppressed by incubation for less than 10 minutes. This suppressed effect was missing with PMA-induced chemiluminescence. On the both fMLP- and PMA-induced chemiluminescence, the priming effect of ibudilast was further enhanced by the treatment with H-7, a protein kinase C inhibitor. In contrast, the priming effect of ibudilast on the fMLP-induced chemiluminescence was abolished by the treatment with ST-638, a selective inhibitor of tyrosine kinase. Ibudilast showed a transient stimulatory effect on cyclic AMP accumulation which continued for only a few minutes. Ibudilast showed no significant effect on phospholipase D dependent chemiluminescence, 1,4,5 trisphosphate level, or protein kinase C activity. Ibudilast inhibited extracellular calcium influx. These results suggest that ibudilast acts on or through tyrosine kinase to achieved its priming effect on the fMLP-induced chemiluminescence. The early and transient increase in cyclic AMP level may explain the inhibitory effect of ibudilast on the fMLP-induced chemiluminescence after short time of incubation.
authors: Department of Pharmacology, Gifu University School of Medicine, Japan.
authors: M
authors: M
authors: Niwa
authors: K
authors: K
authors: Kohno
authors: L Y
authors: LY
authors: al-Essa
authors: M
authors: M
authors: Kobayashi
authors: M
authors: M
authors: Nozaki
authors: K
authors: K
authors: Tsurumi
mesh_terms: D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000097:blood; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D002118:Calcium; D000242:Cyclic AMP; D015544:Inositol 1,4,5-Trisphosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011725:Pyridines; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D014665:Vasodilator Agents; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles