Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via β2-adrenoceptor-dependent and -independent mechanisms

Background β 2 -Adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. Objective We examined whether various widely prescribed β 2 -adrenoceptor agonists differ in anti-inflammatory mechanisms. Methods We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. Results At high concentrations, fenoterol significantly inhibited both N -formyl-methionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective β-adrenoceptor antagonist, or ICI-118551, a β 2 -adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10 −6 M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10 −5 M). Conclusions Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via β 2 -adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.