Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1484–1492. doi: 10.1111/j.1476-5381.1991.tb09815.x

Postjunctional alpha-adrenoceptors in the rabbit isolated distal saphenous artery: indirect sensitivity to prazosin of responses to noradrenaline mediated via postjunctional alpha 2-adrenoceptors.

W R Dunn 1, J C McGrath 1, V G Wilson 1
PMCID: PMC1908394  PMID: 1679360

Abstract

1. Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional alpha 1-adrenoceptors. Prazosin competitively antagonized responses to noradrenaline (NA) with a pA2 value of 8.6, while a relatively high concentration of rauwolscine (1 microM), produced only a 2 fold rightward displacement of the NA cumulative concentration-response curve (CCRC). 2. Despite the fact that angiotensin II (AII) was without effect on responses to NA or phenylephrine in this preparation, this peptide made responses to NA less susceptible to the antagonistic action of prazosin. This was particularly evident on the lower portion of the CCRC for NA. These results suggest that in the presence of AII, NA produces contractile responses by an action mediated through a prazosin-resistant adrenoceptor. 3. An attempt was made to isolate a homogeneous population of postjunctional alpha 2-adrenoceptors by use of a receptor protection procedure involving the combination of rauwolscine and phenoxybenzamine. After the protection protocol no responses were observed to the alpha-adrenoceptor agonists NA, phenylephrine or UK-14304. In the presence of angiotensin II however, concentration-dependent contractions were observed to each of these agonists. Under these conditions the rank order of potency, UK-14304 greater than NA greater than phenylephrine, is consistent with that of an effect mediated through postjunctional alpha 2-adrenoceptors. 4. The responses to NA, after the protection protocol, in the presence of AII, were susceptible to the selective alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), but resistant to the selective alpha 2-adrenoceptor antagonist prazosin (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1484

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. Besse J. C., Furchgott R. F. Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. J Pharmacol Exp Ther. 1976 Apr;197(1):66–78. [PubMed] [Google Scholar]
  3. Cheung D. W. An electrophysiological study of alpha-adrenoceptor mediated excitation-contraction coupling in the smooth muscle cells of the rat saphenous vein. Br J Pharmacol. 1985 Jan;84(1):265–271. [PMC free article] [PubMed] [Google Scholar]
  4. Constantine J. W., Lebel W., Archer R. Functional postsynaptic alpha 2- but not alpha 1-adrenoceptors in dog saphenous vein exposed to phenoxybenzamine. Eur J Pharmacol. 1982 Dec 3;85(3-4):325–329. doi: 10.1016/0014-2999(82)90219-9. [DOI] [PubMed] [Google Scholar]
  5. Daly C. J., Dunn W. R., McGrath J. C., Wilson V. G. An attempt at selective protection from phenoxybenzamine of postjunctional alpha-adrenoceptor subtypes mediating contractions to noradrenaline in the rabbit isolated saphenous vein. Br J Pharmacol. 1988 Oct;95(2):501–511. doi: 10.1111/j.1476-5381.1988.tb11670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daly C. J., McGrath J. C., Wilson V. G. An examination of the postjunctional alpha-adrenoceptor subtypes for (-)-noradrenaline in several isolated blood vessels from the rabbit. Br J Pharmacol. 1988 Oct;95(2):473–484. doi: 10.1111/j.1476-5381.1988.tb11668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daly C. J., McGrath J. C., Wilson V. G. Evidence that the population of postjunctional-adrenoceptors mediating contraction of smooth muscle in the rabbit isolated ear vein is predominantly alpha 2. Br J Pharmacol. 1988 Aug;94(4):1085–1090. doi: 10.1111/j.1476-5381.1988.tb11626.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Mey J., Vanhoutte P. M. Uneven distribution of postjunctional alpha 1-and alpha 2-like adrenoceptors in canine arterial and venous smooth muscle. Circ Res. 1981 Jun;48(6 Pt 1):875–884. doi: 10.1161/01.res.48.6.875. [DOI] [PubMed] [Google Scholar]
  9. Digges K. G., Summers R. J. Characterization of postsynaptic alpha-adrenoceptors in rat aortic strips and portal veins. Br J Pharmacol. 1983 Jul;79(3):655–665. doi: 10.1111/j.1476-5381.1983.tb10002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Docherty J. R., MacDonald A., McGrath J. C. Further sub-classification of alpha-adrenoceptors in the cardiovascular system, vas deferens and anococcygeus of the rat [proceedings]. Br J Pharmacol. 1979 Nov;67(3):421P–422P. [PMC free article] [PubMed] [Google Scholar]
  11. Docherty J. R., McGrath J. C. A comparison of pre- and post-junctional potencies of several alpha-adrenoceptor agonists in the cardiovascular system and anococcygeus muscle of the rat. Evidence for two types of post-junctional alpha-adrenoceptor. Naunyn Schmiedebergs Arch Pharmacol. 1980 Jun;312(2):107–116. doi: 10.1007/BF00569718. [DOI] [PubMed] [Google Scholar]
  12. Drew G. M. What do antagonists tell us about alpha-adrenoceptors? Clin Sci (Lond) 1985;68 (Suppl 10):15s–19s. doi: 10.1042/cs068s015. [DOI] [PubMed] [Google Scholar]
  13. Drew G. M., Whiting S. B. Evidence for two distinct types of postsynaptic alpha-adrenoceptor in vascular smooth muscle in vivo. Br J Pharmacol. 1979 Oct;67(2):207–215. doi: 10.1111/j.1476-5381.1979.tb08668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dunn W. R., Daly C. J., McGrath J. C., Wilson V. G. A comparison of the effects of angiotensin II and Bay K 8644 on responses to noradrenaline mediated via postjunctional alpha 1-and alpha 2-adrenoceptors in rabbit isolated blood vessels. Br J Pharmacol. 1991 Jun;103(2):1475–1483. doi: 10.1111/j.1476-5381.1991.tb09814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dunn W. R., McGrath J. C., Wilson V. G. Expression of functional postjunctional alpha 2-adrenoceptors in rabbit isolated distal saphenous artery--a permissive role for angiotensin II? Br J Pharmacol. 1989 Feb;96(2):259–261. doi: 10.1111/j.1476-5381.1989.tb11810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Faber J. E. In situ analysis of alpha-adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation. Circ Res. 1988 Jan;62(1):37–50. doi: 10.1161/01.res.62.1.37. [DOI] [PubMed] [Google Scholar]
  17. Flavahan N. A., Vanhoutte P. M. Effect of cooling on alpha-1 and alpha-2 adrenergic responses in canine saphenous and femoral veins. J Pharmacol Exp Ther. 1986 Jul;238(1):139–147. [PubMed] [Google Scholar]
  18. Furuta T. Precontraction-induced contractile response of isolated canine portal vein to alpha-2 adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol. 1988 May;337(5):525–530. doi: 10.1007/BF00182726. [DOI] [PubMed] [Google Scholar]
  19. Glusa E., Markwardt F. Characterisation of postjunctional alpha-adrenoceptors in isolated human femoral veins and arteries. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):101–105. doi: 10.1007/BF00634256. [DOI] [PubMed] [Google Scholar]
  20. Grant T. L., McGrath J. C. Interactions between angiotensin II and alpha-adrenoceptor agonists mediating pressor responses in the pithed rat. Br J Pharmacol. 1988 Dec;95(4):1229–1240. doi: 10.1111/j.1476-5381.1988.tb11760.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hieble J. P., Sarau H. M., Foley J. J., Demarinis R. M., Pendleton R. G. Comparison of central and peripheral alpha 1-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):267–273. doi: 10.1007/BF00501164. [DOI] [PubMed] [Google Scholar]
  22. Hieble J. P., Woodward D. F. Different characteristics of postjunctional alpha-adrenoceptors on arterial and venous smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1984 Nov;328(1):44–50. doi: 10.1007/BF00496105. [DOI] [PubMed] [Google Scholar]
  23. Hooker C. S., Calkins P. J., Fleisch J. H. On the measurement of vascular and respiratory smooth muscle responses in vitro. Blood Vessels. 1977;14(1):1–11. doi: 10.1159/000158110. [DOI] [PubMed] [Google Scholar]
  24. Kapocsi J., Somogyi G. T., Ludvig N., Serfozo P., Harsing L. G., Jr, Woods R. J., Vizi E. S. Neurochemical evidence for two types of presynaptic alpha 2-adrenoceptors. Neurochem Res. 1987 Feb;12(2):141–147. doi: 10.1007/BF00979530. [DOI] [PubMed] [Google Scholar]
  25. MacLean M. R., McGrath J. C. Effects of pre-contraction with endothelin-1 on alpha 2-adrenoceptor- and (endothelium-dependent) neuropeptide Y-mediated contractions in the isolated vascular bed of the rat tail. Br J Pharmacol. 1990 Sep;101(1):205–211. doi: 10.1111/j.1476-5381.1990.tb12114.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McGrath J. C. Evidence for more than one type of post-junctional alpha-adrenoceptor. Biochem Pharmacol. 1982 Feb 15;31(4):467–484. doi: 10.1016/0006-2952(82)90147-2. [DOI] [PubMed] [Google Scholar]
  27. Nielsen H., Thom S. M., Hughes A. D., Martin G. N., Mulvany M. J., Sever P. S. Postjunctional alpha 2-adrenoceptors mediate vasoconstriction in human subcutaneous resistance vessels. Br J Pharmacol. 1989 Jul;97(3):829–834. doi: 10.1111/j.1476-5381.1989.tb12022.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Purdy R. E., Weber M. A. Angiotensin II amplification of alpha-adrenergic vasoconstriction: role of receptor reserve. Circ Res. 1988 Oct;63(4):748–757. doi: 10.1161/01.res.63.4.748. [DOI] [PubMed] [Google Scholar]
  29. Rajanayagam M. A., Medgett I. C. Greater activation of smooth muscle alpha-2 adrenoceptors by epinephrine in distal than in proximal segments of rat tail artery. J Pharmacol Exp Ther. 1987 Mar;240(3):989–997. [PubMed] [Google Scholar]
  30. Ruffolo R. R., Jr, Rosing E. L., Waddell J. E. Receptor interactions of imidazolines. I. Affinity and efficacy for alpha adrenergic receptors in rat aorta. J Pharmacol Exp Ther. 1979 Jun;209(3):429–436. [PubMed] [Google Scholar]
  31. Schümann H. J., Lues I. Postjunctional alpha-adrenoceptors in the isolated saphenous vein of the rabbit. Characterization and influence of angiotensin. Naunyn Schmiedebergs Arch Pharmacol. 1983 Aug;323(4):328–334. doi: 10.1007/BF00512471. [DOI] [PubMed] [Google Scholar]
  32. Shepperson N. B. Alpha 2-adrenoceptor agonists potentiate responses mediated by alpha 1-adrenoceptors in the cat nictitating membrane. Br J Pharmacol. 1984 Oct;83(2):463–469. doi: 10.1111/j.1476-5381.1984.tb16508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shoji T., Tsuru H., Shigei T. A regional difference in the distribution of postsynaptic alpha-adrenoceptor subtypes in canine veins. Naunyn Schmiedebergs Arch Pharmacol. 1983 Dec;324(4):246–255. doi: 10.1007/BF00502619. [DOI] [PubMed] [Google Scholar]
  34. Starke K. Alpha-adrenoceptor subclassification. Rev Physiol Biochem Pharmacol. 1981;88:199–236. [PubMed] [Google Scholar]
  35. Sulpizio A., Hieble J. P. Demonstration of alpha 2-adrenoceptor-mediated contraction in the isolated canine saphenous artery treated with Bay K 8644. Eur J Pharmacol. 1987 Mar 3;135(1):107–110. doi: 10.1016/0014-2999(87)90765-5. [DOI] [PubMed] [Google Scholar]
  36. Templeton A. G., Macmillan J., McGrath J. C., Storey N. D., Wilson V. G. Evidence for prazosin-resistant, rauwolscine-sensitive alpha-adrenoceptors mediating contractions in the isolated vascular bed of the rat tail. Br J Pharmacol. 1989 Jun;97(2):563–571. doi: 10.1111/j.1476-5381.1989.tb11986.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Xiao X. H., Rand M. J. Alpha 2-adrenoceptor agonists enhance responses to certain other vasoconstrictor agonists in the rat tail artery. Br J Pharmacol. 1989 Mar;96(3):539–546. doi: 10.1111/j.1476-5381.1989.tb11851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES