Salmeterol is a competitive antagonist at beta-adrenoceptors mediating inhibition of respiratory burst in guinea-pig eosinophils.
The ability of the long-acting beta-adrenoceptor agonists eformoterol and salmeterol to inhibit leukotriene (LT) B4 (100 nM; approximately EC70)-induced hydrogen peroxide (H2O2) generation by guinea-pig peritoneal eosinophils was investigated and compared with salbutamol. Eformoterol and salbutamol produced a concentration-dependent inhibition of LTB4-induced H2O2 generation with pIC50 values of 6.22 and > 5.0 respectively. The inhibitory effect eformoterol was mediated through an interaction with beta-adrenoceptors for it was antagonised by propranolol with an affinity (7.21) that was independent of antagonist concentration (100 nM and 1 microM). In contrast, salmeterol (1 nM to 10 microM) failed to inhibit H2O2 generation at any concentration examined irrespective of the pre-incubation time (0, 0.25, 0.5, 1, 2, 15 or 30 min). Salmeterol did, however, competitively antagonise (slope of Schild plot = 0.91) the inhibition of H2O2 generation induced by eformoterol with a pA2 of 5.9. Possible explanations for the lack of inhibitory effect of salmeterol on LTB4-induced respiratory burst are advanced and critically discussed.
Rabe
K F
KF
Department of Thoracic Medicine, Royal Brompton National Heart and Lung Institute, London, UK.
Giembycz
M A
MA
Dent
G
G
Perkins
R S
RS
Evans
P
P
Barnes
P J
PJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D016897:Respiratory Burst / Q000187:drug effects*; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D007975:Leukotriene B4; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate