Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1980 Nov;10(5):417–423. doi: 10.1111/j.1365-2125.1980.tb01782.x

Tachyphylaxis to beta-adrenoceptor agonists in human bronchial smooth muscle: studies in vitro.

C Davis, M E Conolly
PMCID: PMC1430155  PMID: 6108126

Abstract

In studies on human isolated peripheral airway smooth muscle; 1 A concentration dependent beta-adrenoceptor tachyphylaxis was observed to isoprenaline. 2 Cross desensitization to other beta-adrenoceptor agonists was demonstrated. 3 The desensitization was reversible with time. Hydrocortisone appeared to accelerate the recovery from the desensitized state. Low concentration isoprenaline (10(-9) mol l-1) prevented recovery whereas cyclohexamide 1.8 x 10(-4) mol l-1 had no noticeable effect on recovery. Continued occupancy of the receptor appears to prevent recovery. The recovery from the desensitized state does not apparently require synthesis of new proteins. 4 Bronchial wall cyclic AMP response to isoprenaline was attenuated after isoprenaline induced desensitization whereas total phosphodiesterase activity of bronchial wall was not altered by desensitization. Thus by exclusion the adenylate cyclase receptor complex may be altered in human peripheral airway smooth muscle beta-adrenoceptor tachyphylaxis.

Full text

PDF
417

Selected References

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

  1. Benoy C. J., El-Fellah M. S., Schneider R., Wade O. L. Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo. Br J Pharmacol. 1975 Dec;55(4):547–554. doi: 10.1111/j.1476-5381.1975.tb07431.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Browning E. T., Brostrom C. O., Groppi V. E., Jr Altered adenosine cyclic 3',5'-monophosphate synthesis and degradation by C-6 astrocytoma cells following prolonged exposure to norepinephrine. Mol Pharmacol. 1976 Jan;12(1):32–40. [PubMed] [Google Scholar]
  3. CONSTANTINE J. W. THE SPIRALLY CUT TRACHEAL STRIP PREPARATION. J Pharm Pharmacol. 1965 Jun;17:384–385. doi: 10.1111/j.2042-7158.1965.tb07688.x. [DOI] [PubMed] [Google Scholar]
  4. Choo-Kang Y. F., Simpson W. T., Grant I. W. Controlled comparison of the bronchodilator effects of three beta-adrenergic stimulant drugs administered by inhalation to patients with asthma. Br Med J. 1969 May 3;2(5652):287–289. doi: 10.1136/bmj.2.5652.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conolly M. E., Davies D. S., Dollery C. T., George C. F. Resistance to -adrenoceptor stimulants (a possible explanation for the rise in ashtma deaths). Br J Pharmacol. 1971 Oct;43(2):389–402. [PMC free article] [PubMed] [Google Scholar]
  6. Conolly M. E., Greenacre J. K. The beta-adrenoceptor of the human lymphocyte and human lung parenchyma. Br J Pharmacol. 1977 Jan;59(1):17–23. doi: 10.1111/j.1476-5381.1977.tb06971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fleisch J. H., Titus E. The prevention of isoproterenol desensitization and isoproterenol reversal. J Pharmacol Exp Ther. 1972 Jun;181(3):425–433. [PubMed] [Google Scholar]
  8. Franklin T. J., Foster S. J. Hormone-induced desensitisation of hormonal control of cyclic AMP levels in human diploid fibroblasts. Nat New Biol. 1973 Dec 5;246(153):146–148. doi: 10.1038/newbio246146a0. [DOI] [PubMed] [Google Scholar]
  9. Greenacre J. K., Schofield P., Conolly M. E. Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and asthmatic patients in vitro. Br J Clin Pharmacol. 1978 Mar;5(3):199–206. doi: 10.1111/j.1365-2125.1978.tb01624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holgate S. T., Baldwin C. J., Tattersfield A. E. beta-adrenergic agonist resistance in normal human airways. Lancet. 1977 Aug 20;2(8034):375–377. doi: 10.1016/s0140-6736(77)90304-x. [DOI] [PubMed] [Google Scholar]
  11. Inman W. H., Mushin W. W. Jaundice after repeated exposure to halothane: an analysis of Reports to the Committee on Safety of Medicines. Br Med J. 1974 Jan 5;1(5896):5–10. doi: 10.1136/bmj.1.5896.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Keighley J. F. Iatrogenic asthma associated with adrenergic aerosols. Ann Intern Med. 1966 Nov;65(5):985–995. doi: 10.7326/0003-4819-65-5-985. [DOI] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Larsson S., Svedmyr N., Thiringer G. Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline. J Allergy Clin Immunol. 1977 Feb;59(2):93–100. doi: 10.1016/0091-6749(77)90209-3. [DOI] [PubMed] [Google Scholar]
  15. Logsdon P. J., Middleton E., Jr, Coffey R. G. Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and nonasthmatic subjects. J Allergy Clin Immunol. 1972 Jul;50(1):45–56. doi: 10.1016/0091-6749(72)90078-4. [DOI] [PubMed] [Google Scholar]
  16. Samir Amer M., Kreighbaum W. E. Cyclic nucleotide phosphodiesterases: properties, activators, inhibitors, structure--activity relationships, and possible role in drug development. J Pharm Sci. 1975 Jan;64(1):1–37. doi: 10.1002/jps.2600640106. [DOI] [PubMed] [Google Scholar]
  17. Spilker B., Tyll J. On the question of tachyphylaxis to isoproterenol in guinea pigs. Eur J Pharmacol. 1976 Apr;36(2):283–288. doi: 10.1016/0014-2999(76)90081-9. [DOI] [PubMed] [Google Scholar]
  18. Thompson W. J., Appleman M. M. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Biochemistry. 1971 Jan 19;10(2):311–316. [PubMed] [Google Scholar]
  19. Tinkelman D. G., Avner S. E., Cooper D. M. Assessing bronchodilator responsiveness. J Allergy Clin Immunol. 1977 Feb;59(2):109–114. doi: 10.1016/0091-6749(77)90211-1. [DOI] [PubMed] [Google Scholar]
  20. Weiss B., Hait W. N. Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Annu Rev Pharmacol Toxicol. 1977;17:441–477. doi: 10.1146/annurev.pa.17.040177.002301. [DOI] [PubMed] [Google Scholar]

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

RESOURCES