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. 1991 Jun;103(2):1351–1356. doi: 10.1111/j.1476-5381.1991.tb09792.x

Characterization of catecholamine-mediated relaxations in rat isolated gastric fundus: evidence for an atypical beta-adrenoceptor.

D P McLaughlin 1, A MacDonald 1
PMCID: PMC1908376  PMID: 1679358

Abstract

1. Experiments were carried out in order to characterize the receptors mediating relaxant responses to catecholamines in the rat gastric fundus. The effects of noradrenaline, isoprenaline and the 'atypical' or beta 3-adrenoceptor agonist, BRL 37344, on methacholine-induced tone were measured. Prazosin, propranolol and cyanopindolol were used as antagonists. 2. Relaxant responses to noradrenaline, in the presence of propranolol (1 microM) were antagonized in a concentration-dependent manner by prazosin (0.01 to 1 microM), although this antagonism was weak and non-competitive in nature. Relaxant responses to isoprenaline, in the presence of prazosin (0.1 microM), were antagonized only by the highest concentration of propranolol (1 microM) giving a pKB of 6.3 BRL 37344 also relaxed the rat gastric fundus in the presence of prazosin (0.1 microM), and the responses to BRL 37344 were unaffected by propranolol (1 microM). 3. Tachyphylaxis to BRL 37344 was observed, a second concentration-response curve being significantly shifted to the right. Exposure of tissues to BRL 37344 (1 microM) between concentration-response curves also caused an 11 fold rightward shift in the response to isoprenaline. 4. In the presence of prazosin (0.1 microM) and propranolol (1 microM), the rank order of potency of the agonists was: (-)-isoprenaline (1.0) greater than (-)-noradrenaline (0.39) greater than BRL 37344 (0.10). 5. Responses to BRL 37344 in the presence of prazosin (0.1 microM) and propranolol (1 microM) were antagonized by (+/-)-cyanopindolol (1 microM), with a pKB of 6.56.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  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., Charlton K. G., Clarke D. E. Responses to norepinephrine resistant to inhibition by alpha and beta adrenoceptor antagonists. J Pharmacol Exp Ther. 1986 Feb;236(2):408–415. [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Bowman W. C., Hall M. T. Inhibition of rabbit intestine mediated by alpha- and beta-adrenoceptors. Br J Pharmacol. 1970 Feb;38(2):399–415. doi: 10.1111/j.1476-5381.1970.tb08528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bristow M., Sherrod T. R., Green R. D. Analysis of beta receptor drug interactions in isolated rabbit atrium, aorta, stomach and trachea. J Pharmacol Exp Ther. 1970 Jan;171(1):52–61. [PubMed] [Google Scholar]
  11. Buckner C. K., Christopherson R. C. Adrenergic receptors of rat esophageal smooth muscle. J Pharmacol Exp Ther. 1974 May;189(2):467–475. [PubMed] [Google Scholar]
  12. Challiss R. A., Leighton B., Wilson S., Thurlby P. L., Arch J. R. An investigation of the beta-adrenoceptor that mediates metabolic responses to the novel agonist BRL28410 in rat soleus muscle. Biochem Pharmacol. 1988 Mar 1;37(5):947–950. doi: 10.1016/0006-2952(88)90186-4. [DOI] [PubMed] [Google Scholar]
  13. Croci T., Cecchi R., Tarantino A., Aureggi G., Bianchetti A., Boigegrain R., Manara L. Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents. Pharmacol Res Commun. 1988 Feb;20(2):147–151. doi: 10.1016/s0031-6989(88)80007-9. [DOI] [PubMed] [Google Scholar]
  14. Emorine L. J., Marullo S., Briend-Sutren M. M., Patey G., Tate K., Delavier-Klutchko C., Strosberg A. D. Molecular characterization of the human beta 3-adrenergic receptor. Science. 1989 Sep 8;245(4922):1118–1121. doi: 10.1126/science.2570461. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Gillespie J. S., Khoyi M. A. The site and receptors responsible for the inhibition by sympathetic nerves of intestinal smooth muscle and its parasympathetic motor nerves. J Physiol. 1977 Jun;267(3):767–789. doi: 10.1113/jphysiol.1977.sp011837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grivegnée A. R., Fontaine J., Reuse J. Effect of dopamine on dog distal colon in-vitro. J Pharm Pharmacol. 1984 Jul;36(7):454–457. doi: 10.1111/j.2042-7158.1984.tb04424.x. [DOI] [PubMed] [Google Scholar]
  18. Harms H. H., Zaagsma J., de Vente J. Differentiation of beta-adrenoceptors in right atrium, diaphragm and adipose tissue of the rat, using stereoisomers of propranolol, alprenolol, nifenalol and practolol. Life Sci. 1977 Jul 1;21(1):123–128. doi: 10.1016/0024-3205(77)90432-5. [DOI] [PubMed] [Google Scholar]
  19. Kaumann A. J. Is there a third heart beta-adrenoceptor? Trends Pharmacol Sci. 1989 Aug;10(8):316–320. doi: 10.1016/0165-6147(89)90065-5. [DOI] [PubMed] [Google Scholar]
  20. Kelly J., Macdonald A. Relaxant effects of alpha-adrenoceptor agonists in the rat isolated gastric fundus. J Pharm Pharmacol. 1990 Jan;42(1):30–34. doi: 10.1111/j.2042-7158.1990.tb05344.x. [DOI] [PubMed] [Google Scholar]
  21. Lathrop D. A., Nànàsi P. P., Varrò A. In vitro cardiac models of dog Purkinje fibre triggered and spontaneous electrical activity: effects of nicorandil. Br J Pharmacol. 1990 Jan;99(1):119–123. doi: 10.1111/j.1476-5381.1990.tb14664.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lefebvre R. A., Verplanken P. A., Bogaert M. G. Pharmacological characterization of the postjunctional beta-adrenoceptors in the rat gastric fundus. Eur J Pharmacol. 1984 Oct 30;106(1):1–9. doi: 10.1016/0014-2999(84)90671-x. [DOI] [PubMed] [Google Scholar]
  23. MacDonald A., Kelly J., Dettmar P. W. Pre- and post-junctional alpha-adrenoceptor-mediated responses in the rat gastric fundus in-vitro. J Pharm Pharmacol. 1990 Nov;42(11):752–757. doi: 10.1111/j.2042-7158.1990.tb07015.x. [DOI] [PubMed] [Google Scholar]
  24. MacKay D. How should values of pA2 and affinity constants for pharmacological competitive antagonists be estimated? J Pharm Pharmacol. 1978 May;30(5):312–313. doi: 10.1111/j.2042-7158.1978.tb13237.x. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Norman B. J., Leathard H. L. Evidence that an atypical beta-adrenoceptor mediates the inhibition of spontaneous rhythmical contractions of rabbit isolated jejunum induced by ritodrine and salbutamol. Br J Pharmacol. 1990 Sep;101(1):27–30. doi: 10.1111/j.1476-5381.1990.tb12083.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stanton H. C. Selective metabolic and cardiovascular beta receptor antagonism in the rat. Arch Int Pharmacodyn Ther. 1972 Apr;196(2):246–258. [PubMed] [Google Scholar]
  28. Tan S., Curtis-Prior P. B. Characterization of the beta-adrenoceptor of the adipose cell of the rat. Int J Obes. 1983;7(5):409–414. [PubMed] [Google Scholar]
  29. VANE J. R. A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol Chemother. 1957 Sep;12(3):344–349. doi: 10.1111/j.1476-5381.1957.tb00146.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Verplanken P. A., Lefebvre R. A., Bogaert M. G. Pharmacological characterization of alpha adrenoceptors in the rat gastric fundus. J Pharmacol Exp Ther. 1984 Nov;231(2):404–410. [PubMed] [Google Scholar]
  31. Walter M., Lemoine H., Kaumann A. J. Stimulant and blocking effects of optical isomers of pindolol on the sinoatrial node and trachea of guinea pig. Role of beta-adrenoceptor subtypes in the dissociation between blockade and stimulation. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):159–175. doi: 10.1007/BF00500912. [DOI] [PubMed] [Google Scholar]
  32. Wikberg J. Localization of adrenergic receptors in guinea pig ileum and rabbit jejunum to cholinergic neurons and to smooth muscle cells. Acta Physiol Scand. 1977 Feb;99(2):190–207. doi: 10.1111/j.1748-1716.1977.tb10370.x. [DOI] [PubMed] [Google Scholar]
  33. Wilson C., Wilson S., Piercy V., Sennitt M. V., Arch J. R. The rat lipolytic beta-adrenoceptor: studies using novel beta-adrenoceptor agonists. Eur J Pharmacol. 1984 May 4;100(3-4):309–319. doi: 10.1016/0014-2999(84)90007-4. [DOI] [PubMed] [Google Scholar]
  34. Zaagsma J., Nahorski S. R. Is the adipocyte beta-adrenoceptor a prototype for the recently cloned atypical 'beta 3-adrenoceptor'? Trends Pharmacol Sci. 1990 Jan;11(1):3–7. doi: 10.1016/0165-6147(90)90032-4. [DOI] [PubMed] [Google Scholar]
  35. 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]

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