Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Dec;110(4):1375–1380. doi: 10.1111/j.1476-5381.1993.tb13972.x

Zeneca ZD7114 acts as an antagonist at beta 3-adrenoceptors in rat isolated ileum.

J W Growcott 1, B Holloway 1, M Green 1, C Wilson 1
PMCID: PMC2175874  PMID: 7905770

Abstract

1. The relaxant effects of Zeneca ZD7114, BRL37344 (putative beta 3-adrenoceptor agonists) and various phenylethylamine-based agonists were studied in isolated ileum of the rat where tone was increased with carbachol (0.5 microM). Agonist-induced relaxation.was measured under equilibrium conditions with alpha-, beta 1- and beta 2-adrenoceptors inhibited. 2. Relaxant responses were obtained to isoprenaline, noradrenaline, and BRL37344, although, the efficacy of this latter agent was significantly.lower than that of isoprenaline. Salbutamol caused weak relaxation (< 20%) at high concentrations (10 microM) and ZD7114 was without significant relaxant effect even at high concentrations (10 microM). 3. Relaxant responses to isoprenaline and BRL37344 were weakly antagonized by high concentrations of (+/-)-propranolol (10 and 100 microM) yielding pKB values of 5.7 with isoprenaline as the agonist and 5.5 with BRL37344 as the agonist. 4. The non-selective beta-adrenoceptor antagonist, (+/-)-alprenolol (1-100 microM) caused competitive antagonism of the relaxant responses to isoprenaline (pA2 value = 6.5). A similar pKB value was obtained when BRL37344 was used as the agonist (6.4). 5. Relaxant effects of isoprenaline and BRL37344 were also antagonized by ZD7114 (1-100 microM) yielding pA2 and pKB values of 6.3 and 6.7 respectively. 6. The low potencies of (+/-)-propranolol and (+/-)-alprenolol as antagonists of the relaxant responses to isoprenaline and BRL37344 indicate that both the agonists and antagonists employed in the current study may interact with beta 3-adrenoceptors in the rat isolated ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1375

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arch J. R., Ainsworth A. T., Cawthorne M. A., Piercy V., Sennitt M. V., Thody V. E., Wilson C., Wilson S. Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature. 1984 May 10;309(5964):163–165. doi: 10.1038/309163a0. [DOI] [PubMed] [Google Scholar]
  3. Arch J. R. The brown adipocyte beta-adrenoceptor. Proc Nutr Soc. 1989 Jul;48(2):215–223. doi: 10.1079/pns19890032. [DOI] [PubMed] [Google Scholar]
  4. Bianchetti A., Manara L. In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical beta-adrenoceptors in rat colon. Br J Pharmacol. 1990 Aug;100(4):831–839. doi: 10.1111/j.1476-5381.1990.tb14100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blue D. R., Bond R. A., Adham N., Delmendo R., Michel A. D., Eglen R. M., Whiting R. L., Clarke D. E. Antagonist characterization of atypical beta adrenoceptors in guinea pig ileum: blockade by alprenolol and dihydroalprenolol. J Pharmacol Exp Ther. 1990 Mar;252(3):1034–1042. [PubMed] [Google Scholar]
  6. Bond R. A., Clarke D. E. A response to isoprenaline unrelated to alpha- and beta-adrenoceptor agonism. Br J Pharmacol. 1987 Jul;91(3):683–686. doi: 10.1111/j.1476-5381.1987.tb11262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bond R. A., Clarke D. E. Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the alpha- and beta-subtypes. Br J Pharmacol. 1988 Nov;95(3):723–734. doi: 10.1111/j.1476-5381.1988.tb11698.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Granneman J. G., Lahners K. N., Rao D. D. Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block. Mol Pharmacol. 1992 Dec;42(6):964–970. [PubMed] [Google Scholar]
  9. Growcott J. W., Wilson C., Holloway B., Mainwaring S. Evaluation of ICI D7114, a putative stimulant of brown adipocytes, on histamine-contracted guinea-pig ileum. Br J Pharmacol. 1993 Aug;109(4):1212–1218. doi: 10.1111/j.1476-5381.1993.tb13751.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hollenga C., Haas M., Deinum J. T., Zaagsma J. Discrepancies in lipolytic activities induced by beta-adrenoceptor agonists in human and rat adipocytes. Horm Metab Res. 1990 Jan;22(1):17–21. doi: 10.1055/s-2007-1004839. [DOI] [PubMed] [Google Scholar]
  11. Holloway B. R., Howe R., Rao B. S., Stribling D., Mayers R. M., Briscoe M. G., Jackson J. M. ICI D7114 a novel selective beta-adrenoceptor agonist selectively stimulates brown fat and increases whole-body oxygen consumption. Br J Pharmacol. 1991 Sep;104(1):97–104. doi: 10.1111/j.1476-5381.1991.tb12391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kenakin T. P., Beek D. Is prenalterol (H133/80) really a selective beta 1 adrenoceptor agonist? Tissue selectivity resulting from differences in stimulus-response relationships. J Pharmacol Exp Ther. 1980 May;213(2):406–413. [PubMed] [Google Scholar]
  13. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  14. Liggett S. B. Functional properties of the rat and human beta 3-adrenergic receptors: differential agonist activation of recombinant receptors in Chinese hamster ovary cells. Mol Pharmacol. 1992 Oct;42(4):634–637. [PubMed] [Google Scholar]
  15. McLaughlin D. P., MacDonald A. Evidence for the existence of 'atypical' beta-adrenoceptors (beta 3-adrenoceptors) mediating relaxation in the rat distal colon in vitro. Br J Pharmacol. 1990 Nov;101(3):569–574. doi: 10.1111/j.1476-5381.1990.tb14122.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Taneja D. T., Clarke D. E. Evidence for a noradrenergic innervation to "atypical" beta adrenoceptors (or putative beta-3 adrenoceptors) in the ileum of guinea pig. J Pharmacol Exp Ther. 1992 Jan;260(1):192–200. [PubMed] [Google Scholar]
  17. van der Vliet A., Rademaker B., Bast A. A beta adrenoceptor with atypical characteristics is involved in the relaxation of the rat small intestine. J Pharmacol Exp Ther. 1990 Oct;255(1):218–226. [PubMed] [Google Scholar]

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

RESOURCES