Salmeterol is a competitive antagonist at beta-adrenoceptors mediating inhibition of respiratory burst in guinea-pig eosinophils

Eur J Pharmacol. 1993 Feb 9;231(2):305-8. doi: 10.1016/0014-2999(93)90466-u.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Eosinophils / drug effects
  • Eosinophils / metabolism*
  • Ethanolamines / pharmacology*
  • Formoterol Fumarate
  • Guinea Pigs
  • In Vitro Techniques
  • Leukotriene B4 / antagonists & inhibitors
  • Leukotriene B4 / pharmacology
  • Male
  • Respiratory Burst / drug effects*
  • Salmeterol Xinafoate

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • Leukotriene B4
  • Salmeterol Xinafoate
  • Albuterol
  • Formoterol Fumarate