Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Nov;110(3):1112–1116. doi: 10.1111/j.1476-5381.1993.tb13929.x

Effects of beta-adrenoceptor agonists in human bronchial smooth muscle.

A T Nials 1, R A Coleman 1, M Johnson 1, H Magnussen 1, K F Rabe 1, C J Vardey 1
PMCID: PMC2175821  PMID: 7905340

Abstract

1. We have investigated the potency and duration of action of isoprenaline and a range of beta-adrenoceptor agonists as relaxants of inherent tone in human superfused, isolated bronchial smooth muscle, a tissue reported to contain a homogeneous population of beta 2-adrenoceptors. 2. All of the beta-adrenoceptor agonists caused concentration-related inhibition of inherent tone, with isoprenaline having an EC50 of 27 nM. The rank order of agonist potency was: formoterol > or = -salmeterol > or = clenbuterol > fenoterol = isoprenaline > terbutaline > or = salbutamol > quinprenaline. 3. Relaxant responses to salmeterol were fully reversed by the selective beta 2-adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of beta 2-adrenoceptors. 4. Rt50, i.e. the time taken for 50% recovery from the effects of an EC50 concentration of agonist, differed considerably between the different beta 2-adrenoceptor agonists. Most agonists were short-acting, having Rt50 values less than 13 min. Quinprenaline was of moderate duration, with an Rt50 value of > or = 20 min. In contrast, salmeterol was extremely long-acting, with no sign of recovery within 4 h. 5. Estimates of relative potency and duration of action were similar to those previously determined for these agonists in the guinea-pig isolated trachea. These results suggest, therefore, that guinea-pig trachea is a suitable alternative to human bronchus for the evaluation of the actions of beta-adrenoceptor agonists on airways smooth muscle.

Full text

PDF
1112

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apperley E., Humphrey P. P., Levy G. P. Receptors for 5-hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta. Br J Pharmacol. 1976 Oct;58(2):211–221. doi: 10.1111/j.1476-5381.1976.tb10398.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball D. I., Brittain R. T., Coleman R. A., Denyer L. H., Jack D., Johnson M., Lunts L. H., Nials A. T., Sheldrick K. E., Skidmore I. F. Salmeterol, a novel, long-acting beta 2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo. Br J Pharmacol. 1991 Nov;104(3):665–671. doi: 10.1111/j.1476-5381.1991.tb12486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chideckel E. W., Frost J. L., Mike P., Fedan J. S. The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species. Br J Pharmacol. 1987 Nov;92(3):609–614. doi: 10.1111/j.1476-5381.1987.tb11363.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coleman R. A., Farmer J. B. The inducement of tone and its inhibition in isolated tracheal muscle. J Pharm Pharmacol. 1971 Mar;23(3):220–222. doi: 10.1111/j.2042-7158.1971.tb08648.x. [DOI] [PubMed] [Google Scholar]
  5. Coleman R. A., Nials A. T. Novel and versatile superfusion system. Its use in the evaluation of some spasmogenic and spasmolytic agents using guinea-pig isolated tracheal smooth muscle. J Pharmacol Methods. 1989 Mar;21(1):71–86. doi: 10.1016/0160-5402(89)90023-5. [DOI] [PubMed] [Google Scholar]
  6. Farmer J. B., Farrar D. G., Wilson J. The effect of indomethacin on the tracheal smooth muscle of the guinea-pig. Br J Pharmacol. 1972 Nov;46(3):536P–537P. [PMC free article] [PubMed] [Google Scholar]
  7. Foster R. W. The nature of the adrenergic receptors of the trachea of the guinea-pig. J Pharm Pharmacol. 1966 Jan;18(1):1–12. doi: 10.1111/j.2042-7158.1966.tb07764.x. [DOI] [PubMed] [Google Scholar]
  8. Goldie R. G., Paterson J. W., Spina D., Wale J. L. Classification of beta-adrenoceptors in human isolated bronchus. Br J Pharmacol. 1984 Apr;81(4):611–615. doi: 10.1111/j.1476-5381.1984.tb16125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ito Y., Suzuki H., Aizawa H., Hakoda H., Hirose T. The spontaneous electrical and mechanical activity of human bronchial smooth muscle: its modulation by drugs. Br J Pharmacol. 1989 Dec;98(4):1249–1260. doi: 10.1111/j.1476-5381.1989.tb12671.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jack D. The 1990 Lilly Prize Lecture. A way of looking at agonism and antagonism: lessons from salbutamol, salmeterol and other beta-adrenoceptor agonists. Br J Clin Pharmacol. 1991 May;31(5):501–514. doi: 10.1111/j.1365-2125.1991.tb05571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Löfdahl C. G., Svedmyr N. Formoterol fumarate, a new beta 2-adrenoceptor agonist. Acute studies of selectivity and duration of effect after inhaled and oral administration. Allergy. 1989 May;44(4):264–271. doi: 10.1111/j.1398-9995.1989.tb01068.x. [DOI] [PubMed] [Google Scholar]
  12. Nials A. T., Sumner M. J., Johnson M., Coleman R. A. Investigations into factors determining the duration of action of the beta 2-adrenoceptor agonist, salmeterol. Br J Pharmacol. 1993 Feb;108(2):507–515. doi: 10.1111/j.1476-5381.1993.tb12833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ullman A., Svedmyr N. Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax. 1988 Sep;43(9):674–678. doi: 10.1136/thx.43.9.674. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES