In vitro stimulation of neutrophil motility by metoprolol and sotalol related to inhibition of both H2O2 production and peroxidase mediated iodination of the cell and leucoattractant.
The effects of the beta-receptor blockading agents, metoprolol and sotalol on neutrophil random motility, chemotaxis, post-phagocytic glycolysis, superoxide production, hexose monophosphate shunt activity, myeloperoxidase (MPO) mediated protein iodination and hydrogen peroxide production were assessed in vitro. The concentration range investigated was 10(-8)--10(-2) M for each drug. Both agents caused significant stimulation of neutrophil motility at concentrations of more than 10(-4) M. Increased migration was not associated with increased glycolysis or significant cyclic nucleotide fluctuations, but was inversely related to inhibition of superoxide and hydrogen peroxide generation and MPO mediated iodination with both drugs. In a further series of experiments to determine the relationship between the drug induced inhibition of H2O2 production and MPO mediated protein iodination to stimulation of motility it was found that concentrations of sotalol and metoprolol that caused these effects prevented HRP/H2O2/I- induced inactivation of the leucoattractant and inhibition of neutrophil chemotactic responsiveness. Neither drug inhibited the activity of MPO per se nor the reduction of ferricytochrome c by superoxide generated by the xanthine: xanthine oxidase system in vitro. It is suggested that enhanced neutrophil motility is not related to beta-receptor blockade but rather to restricting the availability of hydrogen peroxide and reactive products of the MPO/H2O2/halide system.
D002465:Cell Movement / Q000187:drug effects; D006735:Horseradish Peroxidase / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D007454:Iodides / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology*; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism; D010587:Phagocytosis; D011412:Propanolamines / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology*; D013481:Superoxides / Q000096:biosynthesis
D007454:Iodides; D008070:Lipopolysaccharides; D009842:Oligopeptides; D011412:Propanolamines; D013481:Superoxides; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013015:Sotalol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D010544:Peroxidases; D008790:Metoprolol