Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms.
BACKGROUND
Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity.


OBJECTIVE
We examined whether various widely prescribed beta2-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-formylmethionyl-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 beta-adrenoceptor antagonist, or ICI-118551, a beta2-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 beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.
Mirza
Zafar Nazir
ZN
Department of Pediatrics, Gunma University School of Medicine, Japan.
Kato
Masahiko
M
Kimura
Hirokazu
H
Tachibana
Atsushi
A
Fujiu
Toru
T
Suzuki
Masato
M
Mochizuki
Hiroyuki
H
Tokuyama
Kenichi
K
Morikawa
Akihiro
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005280:Fenoterol / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017265:Procaterol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D016166:Free Radical Scavengers; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013481:Superoxides; D005280:Fenoterol; C026777:ICI 118551; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D013755:Tetradecanoylphorbol Acetate; D000420:Albuterol; D017265:Procaterol