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

https://doi.org/10.1016/0014-2999(93)90466-UGet rights and content

Abstract

The ability of the long-acting β-adrenoceptor agonists eformoterol and salmeterol to inhibit leukotriene (LT) B4 (100 nM; ∼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 β-adrenoceptors for it was antagonised by propranolol with affinity (7.21) that was independent of antagonist cencentration (100 nM and 1 μM). In contrast, salmeterol (1 nM to 10 μM) failed to inhibit H2O2 generation at any concentration examined irrespective of the pre-incubation time (0, 0.25, 0.5, 1, 2, 5, 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.

References (15)

  • O.P. Twentyman et al.

    Protection against allergen-induced asthma by salmeterol

    Lancet

    (1990)
  • D.I. Ball et al.

    In vitro characterization of the β2-adrenoceptor agonist, salmeterol

    Br. J. Pharmacol.

    (1987)
  • D.I. Ball et al.

    Salmeterol, a novel, long-acting β2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo

    Br. J. Pharmacol.

    (1991)
  • P.R. Butchers et al.

    Salmeterol, a potent and long-acting inhibitor of inflammatory mediator release from human lung

    Br. J. Pharmacol.

    (1991)
  • G. Dent et al.

    Inhibition of eosinophil cyclic nucleotide PDE activity and opsonised zymosan-induced respiratory burst by ‘type IV’-selective PDE inhibitors

    Br. J. Pharmacol.

    (1991)
  • J.G. Dougall et al.

    Estimation of the efficacy and affinity of the β2-adrenoceptor agonist salmeterol in guinea-pig trachea

    Br. J. Pharmacol.

    (1991)
  • I. Gartner

    Separation of human eosinophils in density gradients of polyvinylpyrroline-coated silica gel

    Immunology

    (1980)
There are more references available in the full text version of this article.

Cited by (0)

1

Present address: Krankenhaus Groβhansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Germany.

View full text