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. 1993 Feb;108(2):484–489. doi: 10.1111/j.1476-5381.1993.tb12829.x

The affinity of betaxolol, a beta 1-adrenoceptor-selective blocking agent, for beta-adrenoceptors in the bovine trachea and heart.

E Satoh 1, A Narimatsu 1, Y Hosohata 1, H Tsuchihashi 1, T Nagatomo 1
PMCID: PMC1908007  PMID: 8383566

Abstract

1. The specificity of betaxolol, a beta-adrenoceptor antagonist, for beta 1- and beta 2-adrenoceptors was compared with that of other beta-antagonists, atenolol, ICI-118551, butoxamine and (+/-)-propranolol, in the bovine trachea and heart by competitive interaction with [3H]-CGP12177 as a radioligand. 2. The radioligand Kd values were 0.75 +/- 0.12 and 1.60 +/- 0.11 nM in the trachea and heart, respectively, and the Bmax values were 34.00 +/- 4.41 and 21.54 +/- 2.94 fmol mg-1 protein, respectively. 3. Using ICI-118551, we determined the ratio of beta 1:beta 2-adrenoceptors in the trachea and heart to be approximately 29:71 and 56:44, respectively. 4. In the trachea, a beta 2-predominant tissue, betaxolol and atenolol were more selective for beta 1-adrenoceptor binding sites than beta 2-adrenoceptor binding sites, whereas ICI-118551 and butoxamine were more selective for beta 2-adrenoceptor binding sites. 5. The beta 1-selectivity of betaxolol was 2.2 and 2.7 fold higher than that of atenolol in the bovine trachea and heart. These findings suggest that betaxolol may be useful in the treatment of hypertension, cardiac arrhythmia and angina pectoris.

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Selected References

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  1. Barnes P. J., Nadel J. A., Skoogh B. E., Roberts J. M. Characterization of beta adrenoceptor subtypes in canine airway smooth muscle by radioligand binding and physiological responses. J Pharmacol Exp Ther. 1983 May;225(2):456–461. [PubMed] [Google Scholar]
  2. Bjørnerheim R., Golf S., Hansson V. Apparent lack of beta 2 adrenergic receptors in porcine myocardium. Cardiovasc Res. 1989 Jul;23(7):577–583. doi: 10.1093/cvr/23.7.577. [DOI] [PubMed] [Google Scholar]
  3. Boudot J. P., Cavero I., Fénard S., Lefèvre-Borg F., Manoury P., Roach A. G. Preliminary studies on SL 75212, a new potent cardioselective beta-adrenoceptor antagonist [proceedings]. Br J Pharmacol. 1979 Jul;66(3):445P–445P. [PMC free article] [PubMed] [Google Scholar]
  4. Davis P. B., Silski C. L., Kercsmar C. M., Infeld M. Beta-adrenergic receptors on human tracheal epithelial cells in primary culture. Am J Physiol. 1990 Jan;258(1 Pt 1):C71–C76. doi: 10.1152/ajpcell.1990.258.1.C71. [DOI] [PubMed] [Google Scholar]
  5. Engel G., Hoyer D., Berthold R., Wagner H. (+/-)[125Iodo] cyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig. Naunyn Schmiedebergs Arch Pharmacol. 1981;317(4):277–285. doi: 10.1007/BF00501307. [DOI] [PubMed] [Google Scholar]
  6. Hedberg A., Minneman K. P., Molinoff P. B. Differential distribution of beta-1 and beta-2 adrenergic receptors in cat and guinea-pig heart. J Pharmacol Exp Ther. 1980 Mar;212(3):503–508. [PubMed] [Google Scholar]
  7. Heitz A., Schwartz J., Velly J. Beta-adrenoceptors of the human myocardium: determination of beta 1 and beta 2 subtypes by radioligand binding. Br J Pharmacol. 1983 Dec;80(4):711–717. doi: 10.1111/j.1476-5381.1983.tb10062.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Henry P. J., Rigby P. J., Goldie R. G. Distribution of beta 1- and beta 2-adrenoceptors in mouse trachea and lung: a quantitative autoradiographic study. Br J Pharmacol. 1990 Jan;99(1):136–144. doi: 10.1111/j.1476-5381.1990.tb14667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnsson G., Svedmyr N., Thiringer G. Effects of intravenous propranolol and metoprolol and their interaction with isoprenaline on pulmonary function, heart rate and blood pressure in asthmatics. Eur J Clin Pharmacol. 1975 Apr 4;8(3-4):175–180. doi: 10.1007/BF00567111. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  12. Neve K. A., McGonigle P., Molinoff P. B. Quantitative analysis of the selectivity of radioligands for subtypes of beta adrenergic receptors. J Pharmacol Exp Ther. 1986 Jul;238(1):46–53. [PubMed] [Google Scholar]
  13. Palminteri R., Kaik G. Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol. Eur J Clin Pharmacol. 1983;24(6):741–745. doi: 10.1007/BF00607080. [DOI] [PubMed] [Google Scholar]
  14. Popovich K. J., Hiller C., Hough A., Norris J. S., Cornett L. E. Characterization of a beta-adrenergic receptor in porcine trachealis muscle. Am J Physiol. 1984 Nov;247(5 Pt 1):C342–C349. doi: 10.1152/ajpcell.1984.247.5.C342. [DOI] [PubMed] [Google Scholar]
  15. Pringle T. H., Riddell J. G., Shanks R. G. A comparison of the cardioselectivity of five beta-adrenoceptor blocking drugs. J Cardiovasc Pharmacol. 1987 Aug;10(2):228–237. doi: 10.1097/00005344-198708000-00014. [DOI] [PubMed] [Google Scholar]
  16. Rimele T. J., Henry D. E., Giesa F. R., Buckley S. K., Geiger G., Heaslip R. J., Lee D. K., Grimes D. Comparison of the beta-adrenoceptor affinity and selectivity of cetamolol, atenolol, betaxolol, and ICI-118,551. J Cardiovasc Pharmacol. 1988 Aug;12(2):208–217. doi: 10.1097/00005344-198808000-00011. [DOI] [PubMed] [Google Scholar]
  17. Singh B. N., Whitlock R. M., Comber R. H., Williams F. H., Harris E. A. Effects of cardioselective beta adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma. Clin Pharmacol Ther. 1976 May;19(5 Pt 1):493–501. doi: 10.1002/cpt1976195part1493. [DOI] [PubMed] [Google Scholar]
  18. Tsuchihashi H., Nagatomo T. Binding characteristics of 125I-iodocyanopindolol to beta-adrenergic receptors: biphasic Scatchard plots. II. Effects of selective antagonists. Chem Pharm Bull (Tokyo) 1987 Aug;35(8):3425–3432. doi: 10.1248/cpb.35.3425. [DOI] [PubMed] [Google Scholar]
  19. Tsuchihashi H., Nagatomo T. Binding characteristics of 3H-dihydroalprenolol to beta-adrenergic receptors of rat brain: influence of exo- and endo-glycosidases and glycopeptidase. Jpn J Pharmacol. 1985 Aug;38(4):403–409. doi: 10.1254/jjp.38.403. [DOI] [PubMed] [Google Scholar]
  20. Tsuchihashi H., Nagatomo T. Binding characteristics of 3H-dihydroalprenolol to beta-adrenergic receptors of rat brain: influence of lectins. Jpn J Pharmacol. 1985 Jun;38(2):121–125. doi: 10.1254/jjp.38.121. [DOI] [PubMed] [Google Scholar]
  21. Tsuchihashi H., Nagatomo T. Biphasic binding of 125I-iodocyanopindolol to beta-adrenergic receptors in rat cerebral cortical membranes. I. Assessment by the use of agonists. Chem Pharm Bull (Tokyo) 1987 Jul;35(7):2966–2972. doi: 10.1248/cpb.35.2966. [DOI] [PubMed] [Google Scholar]
  22. Tsuchihashi H., Nagatomo T. Characterization of 3H-dihydroalprenolol binding to beta-adrenergic receptors of rat brain: two binding sites of racemic propranolol in displacement experiments. Chem Pharm Bull (Tokyo) 1987 Jul;35(7):2979–2984. doi: 10.1248/cpb.35.2979. [DOI] [PubMed] [Google Scholar]
  23. Tsuchihashi H., Nagatomo T., Imai S. Three binding sites of 125I-iodocyanopindolol, i.e. beta 1, beta 2-adrenergic and 5HT1B-serotonergic receptors in rat brain determined by the displacement and Scatchard analysis. J Pharmacobiodyn. 1989 Sep;12(9):509–516. doi: 10.1248/bpb1978.12.509. [DOI] [PubMed] [Google Scholar]
  24. Tsuchihashi H., Nagatomo T. Influence of polymeric effectors on binding of 3H-dihydroalprenolol to beta-adrenergic receptor of rat brain. Jpn J Pharmacol. 1985 May;38(1):17–23. doi: 10.1254/jjp.38.17. [DOI] [PubMed] [Google Scholar]
  25. Tsuchihashi H., Nakashima Y., Kinami J., Nagatomo T. Characteristics of 125I-iodocyanopindolol binding to beta-adrenergic and serotonin-1B receptors of rat brain: selectivity of beta-adrenergic agents. Jpn J Pharmacol. 1990 Feb;52(2):195–200. doi: 10.1254/jjp.52.195. [DOI] [PubMed] [Google Scholar]
  26. Tsuchihashi H., Sasaki M., Nagatomo T. Binding characteristics of [3H]dihydroalprenolol to beta-adrenergic receptors of rat brain: comparison with those of rat heart treated with neuraminidase. Chem Pharm Bull (Tokyo) 1985 Sep;33(9):3972–3976. doi: 10.1248/cpb.33.3972. [DOI] [PubMed] [Google Scholar]
  27. Tsuchihashi H., Yokoyama H., Nagatomo T. Binding characteristics of 3H-CGP12177 to beta-adrenoceptors in rat myocardial membranes. Jpn J Pharmacol. 1989 Jan;49(1):11–19. doi: 10.1254/jjp.49.11. [DOI] [PubMed] [Google Scholar]
  28. Vago T., Bevilacqua M., Dagani R., Meroni R., Frigeni G., Santoliss C., Norbiato G. Comparison of rat and human left ventricle beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding. Biochem Biophys Res Commun. 1984 May 31;121(1):346–354. doi: 10.1016/0006-291x(84)90729-0. [DOI] [PubMed] [Google Scholar]
  29. Wellstein A., Palm D., Belz G. G. Affinity and selectivity of beta-adrenoceptor antagonists in vitro. J Cardiovasc Pharmacol. 1986;8 (Suppl 11):S36–S40. doi: 10.1097/00005344-198511001-00006. [DOI] [PubMed] [Google Scholar]

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