Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Dec;95(4):1031–1038. doi: 10.1111/j.1476-5381.1988.tb11736.x

The interaction of methoctramine and himbacine at atrial, smooth muscle and endothelial muscarinic receptors in vitro.

R M Eglen 1, W W Montgomery 1, I A Dainty 1, L K Dubuque 1, R L Whiting 1
PMCID: PMC1854290  PMID: 3219478

Abstract

1. The action of methoctramine and himbacine at muscarinic receptors has been studied using guinea-pig isolated trachea, oesophageal muscularis mucosae, paced left atria, and rat aortic preparations. 2. Methoctramine (1 x 10(-6)-3.2 x 10(-4) M), but not himbacine, elicited positive inotropic responses. These responses were enhanced by pretreating the animals with reserpine. The responses in reserpine-treated animals were not antagonized by phentolamine (1 x 10(-6) M) but were antagonized by propranolol (1 x 10(-6) M). 3. Methoctramine, but not himbacine, exhibited allosteric inhibitory effects at cardiac muscarinic receptors, resulting in a curvilinear Schild plot. Deviations from competitive antagonism were also observed in combination dose-ratio experiments using atropine and methoctramine. At 1 x 10(-6) M, the pKB value for methoctramine was 7.88 +/- 0.15 (mean +/- s.e.mean, n = 5). The pA2 value for himbacine at cardiac muscarinic receptors was 8.52 +/- 0.06 (n = 3). 4. At tracheal and oesophageal muscularis mucosal smooth muscle receptors, the Schild plots for both antagonists were linear. The pA2 values for methoctramine at receptors in these two preparations were similar (6.08 +/- 0.05 and 6.03 +/- 0.09 respectively, n = 4) and were approximately 60 fold less than those values observed at atrial receptors. Himbacine, also exhibited similar values at muscarinic receptors in the trachea and oesophageal muscularis mucosae (7.61 +/- 0.05 and 7.57 +/- 0.04 respectively, n = 4). 5. Muscarinic receptors mediating relaxation of the rat aortic endothelium exhibited pA2 values for methoctramine (5.87 +/- 0.12, n = 6) which were similar to those observed in the smooth muscle, but not the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1031

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. Anwar-ul S., Gilani H., Cobbin L. B. The cardio-selectivity of himbacine: a muscarine receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jan;332(1):16–20. doi: 10.1007/BF00633191. [DOI] [PubMed] [Google Scholar]
  3. Barlow R. B., Burston K. N., Vis A. Three types of muscarinic receptors? [proceedings]. Br J Pharmacol. 1980 Jan;68(1):141P–142P. [PMC free article] [PubMed] [Google Scholar]
  4. Chess-Williams R. G., Broadley K. J., Sheridan D. J. Calculated and actual changes in beta-adrenoceptor number associated with increases in rat and guinea-pig cardiac sensitivity. J Pharm Pharmacol. 1986 Dec;38(12):902–906. doi: 10.1111/j.2042-7158.1986.tb03380.x. [DOI] [PubMed] [Google Scholar]
  5. Choo L. K., Malta E., Mitchelson F. The affinity of some selective muscarinic receptor antagonists for the muscarinic receptor mediating endothelial-dependent relaxation of the rabbit and rat thoracic aorta. J Pharm Pharmacol. 1986 Nov;38(11):843–845. doi: 10.1111/j.2042-7158.1986.tb04507.x. [DOI] [PubMed] [Google Scholar]
  6. Clague R. U., Eglen R. M., Strachan A. C., Whiting R. L. Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro. Br J Pharmacol. 1985 Sep;86(1):163–170. doi: 10.1111/j.1476-5381.1985.tb09446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eglen R. M., Whiting R. L. Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701–707. doi: 10.1111/j.1476-5381.1987.tb11223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eglen R. M., Whiting R. L. Determination of the muscarinic receptor subtype mediating vasodilatation. Br J Pharmacol. 1985 Jan;84(1):3–5. [PMC free article] [PubMed] [Google Scholar]
  9. Eglen R. M., Whiting R. L. Muscarinic receptor subtypes: a critique of the current classification and a proposal for a working nomenclature. J Auton Pharmacol. 1986 Dec;6(4):323–346. doi: 10.1111/j.1474-8673.1986.tb00661.x. [DOI] [PubMed] [Google Scholar]
  10. Emmerson J., Mackay D. The zig-zag tracheal strip. J Pharm Pharmacol. 1979 Nov;31(11):798–798. doi: 10.1111/j.2042-7158.1979.tb13666.x. [DOI] [PubMed] [Google Scholar]
  11. Hynes M. R., Banner W., Jr, Yamamura H. I., Duckles S. P. Characterization of muscarinic receptors of the rabbit ear artery smooth muscle and endothelium. J Pharmacol Exp Ther. 1986 Jul;238(1):100–105. [PubMed] [Google Scholar]
  12. Kamikawa Y., Uchida K., Shimo Y. Heterogeneity of muscarinic receptors in the guinea pig esophageal muscularis mucosae and ileal longitudinal muscle. Gastroenterology. 1985 Mar;88(3):706–716. doi: 10.1016/0016-5085(85)90141-6. [DOI] [PubMed] [Google Scholar]
  13. Leung E., Mitchelson F. Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig. Eur J Pharmacol. 1982 May 7;80(1):11–17. doi: 10.1016/0014-2999(82)90172-8. [DOI] [PubMed] [Google Scholar]
  14. Melchiorre C., Cassinelli A., Quaglia W. Differential blockade of muscarinic receptor subtypes by polymethylene tetraamines. Novel class of selective antagonists of cardiac M-2 muscarinic receptors. J Med Chem. 1987 Jan;30(1):201–204. doi: 10.1021/jm00384a034. [DOI] [PubMed] [Google Scholar]
  15. Michel A. D., Whiting R. L. Direct binding studies on ileal and cardiac muscarinic receptors. Br J Pharmacol. 1987 Dec;92(4):755–767. doi: 10.1111/j.1476-5381.1987.tb11379.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Michel A. D., Whiting R. L. Methoctramine reveals heterogeneity of M2 muscarinic receptors in longitudinal ileal smooth muscle membranes. Eur J Pharmacol. 1988 Jan 19;145(3):305–311. doi: 10.1016/0014-2999(88)90434-7. [DOI] [PubMed] [Google Scholar]
  17. Micheletti R., Montagna E., Giachetti A. AF-DX 116, a cardioselective muscarinic antagonist. J Pharmacol Exp Ther. 1987 May;241(2):628–634. [PubMed] [Google Scholar]
  18. Nedoma J., Dorofeeva N. A., Tucek S., Shelkovnikov S. A., Danilov A. F. Interaction of the neuromuscular blocking drugs alcuronium, decamethonium, gallamine, pancuronium, ritebronium, tercuronium and d-tubocurarine with muscarinic acetylcholine receptors in the heart and ileum. Naunyn Schmiedebergs Arch Pharmacol. 1985 Apr;329(2):176–181. doi: 10.1007/BF00501209. [DOI] [PubMed] [Google Scholar]
  19. PATON W. D., RANG H. P. THE UPTAKE OF ATROPINE AND RELATED DRUGS BY INTESTINAL SMOOTH MUSCLE OF THE GUINEA-PIG IN RELATION TO ACETYLCHOLINE RECEPTORS. Proc R Soc Lond B Biol Sci. 1965 Aug 24;163:1–44. doi: 10.1098/rspb.1965.0058. [DOI] [PubMed] [Google Scholar]
  20. Rubanyi G. M., McKinney M., Vanhoutte P. M. Biphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptors. J Pharmacol Exp Ther. 1987 Mar;240(3):802–808. [PubMed] [Google Scholar]
  21. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  22. Yamanaka K., Hashimoto S., Muramatsu I. Species difference in the muscarinic receptors of thoracic aorta. J Pharmacol Exp Ther. 1986 Jun;237(3):980–986. [PubMed] [Google Scholar]

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

RESOURCES