Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jan;117(1):93–98. doi: 10.1111/j.1476-5381.1996.tb15159.x

(-)-CGP 12177-induced increase of human atrial contraction through a putative third beta-adrenoceptor.

A J Kaumann 1
PMCID: PMC1909374  PMID: 8825348

Abstract

1. The inotropic effects of (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one ((-)-CGP 12177), an antagonist for beta 1- and beta 2-adrenoceptors as well as an agonist for beta 3-adrenoceptors, were investigated on paced preparations of isolated right atrial appendages obtained from patients without advanced heart failure undergoing open heart surgery. 2. In the presence of (-)-propranolol (200 nM), (-)-CGP 12177 increased contractile force with a -log EC50, M, of 7.3. The maximum effects of (-)-CGP 12177 amounted to 15% and 11% of the effects of (-)-isoprenaline (400 microM) and of CaCl2 (6.75 mM) respectively. 3. (-)-Bupranolol 1 microM, an antagonist with a pKB of approximately 7.5 for beta 3-adrenoceptors, antagonized surmountably the positive inotropic effects of (-)-CGP 12177 (in the presence of 200 nM (-)-propranolol) with an apparent pKB of 7.3. 4. The potent positive inotropic effects of (-)-CGP 12177 and their resistance to blockade by (-)-propranolol but antagonism by (-)-bupranolol are consistent with the existence in human atrial myocardium of a minor third beta-adrenoceptor population, possibly related to beta 3-adrenoceptors.

Full text

PDF
93

Selected References

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

  1. Arch J. R., Kaumann A. J. Beta 3 and atypical beta-adrenoceptors. Med Res Rev. 1993 Nov;13(6):663–729. doi: 10.1002/med.2610130604. [DOI] [PubMed] [Google Scholar]
  2. Blin N., Camoin L., Maigret B., Strosberg A. D. Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor. Mol Pharmacol. 1993 Dec;44(6):1094–1104. [PubMed] [Google Scholar]
  3. Blin N., Nahmias C., Drumare M. F., Strosberg A. D. Mediation of most atypical effects by species homologues of the beta 3-adrenoceptor. Br J Pharmacol. 1994 Jul;112(3):911–919. doi: 10.1111/j.1476-5381.1994.tb13167.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blinks J. R. Convenient apparatus for recording contractions of isolated heart muscle. J Appl Physiol. 1965 Jul;20(4):755–757. doi: 10.1152/jappl.1965.20.4.755. [DOI] [PubMed] [Google Scholar]
  5. Blinks J. R. Evaluation of the cardiac effects of several beta adrenergic blocking agents. Ann N Y Acad Sci. 1967 Feb 10;139(3):673–685. doi: 10.1111/j.1749-6632.1967.tb41237.x. [DOI] [PubMed] [Google Scholar]
  6. Blinks J. R. Field stimulation as a means of effecting the graded release of autonomic transmitters in isolated heart muscle. J Pharmacol Exp Ther. 1966 Feb;151(2):221–235. [PubMed] [Google Scholar]
  7. Chambers J., Park J., Cronk D., Chapman C., Kennedy F. R., Wilson S., Milligan G. Beta 3-adrenoceptor agonist-induced down-regulation of Gs alpha and functional desensitization in a Chinese hamster ovary cell line expressing a beta 3-adrenoceptor refractory to down-regulation. Biochem J. 1994 Nov 1;303(Pt 3):973–978. doi: 10.1042/bj3030973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chaudhry A., Granneman J. G. Influence of cell type upon the desensitization of the beta 3-adrenergic receptor. J Pharmacol Exp Ther. 1994 Dec;271(3):1253–1258. [PubMed] [Google Scholar]
  9. 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]
  10. Gille E., Lemoine H., Ehle B., Kaumann A. J. The affinity of (-)-propranolol for beta 1- and beta 2-adrenoceptors of human heart. Differential antagonism of the positive inotropic effects and adenylate cyclase stimulation by (-)-noradrenaline and (-)-adrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1985 Oct;331(1):60–70. doi: 10.1007/BF00498852. [DOI] [PubMed] [Google Scholar]
  11. Granneman J. G. Effects of agonist exposure on the coupling of beta 1 and beta 3 adrenergic receptors to adenylyl cyclase in isolated adipocytes. J Pharmacol Exp Ther. 1992 May;261(2):638–642. [PubMed] [Google Scholar]
  12. Granneman J. G., Lahners K. N. Analysis of human and rodent beta 3-adrenergic receptor messenger ribonucleic acids. Endocrinology. 1994 Sep;135(3):1025–1031. doi: 10.1210/endo.135.3.8070345. [DOI] [PubMed] [Google Scholar]
  13. Granneman J. G., Lahners K. N., Chaudhry A. Characterization of the human beta 3-adrenergic receptor gene. Mol Pharmacol. 1993 Aug;44(2):264–270. [PubMed] [Google Scholar]
  14. Hall J. A., Kaumann A. J., Brown M. J. Selective beta 1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through beta 2-adrenoceptors in human atrial myocardium. Circ Res. 1990 Jun;66(6):1610–1623. doi: 10.1161/01.res.66.6.1610. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kaumann A. J., Blinks J. R. beta-Adrenoceptor blocking agents as partial agonists in isolated heart muscle: dissociation of stimulation and blockade. Naunyn Schmiedebergs Arch Pharmacol. 1980 Apr;311(3):237–248. doi: 10.1007/BF00569403. [DOI] [PubMed] [Google Scholar]
  17. Kaumann A. J., Hall J. A., Murray K. J., Wells F. C., Brown M. J. A comparison of the effects of adrenaline and noradrenaline on human heart: the role of beta 1- and beta 2-adrenoceptors in the stimulation of adenylate cyclase and contractile force. Eur Heart J. 1989 Jun;10 (Suppl B):29–37. doi: 10.1093/eurheartj/10.suppl_b.29. [DOI] [PubMed] [Google Scholar]
  18. Kaumann A. J. Herz-beta-Rezeptoren--Experimentelle Standpunkte. Z Kardiol. 1983 Feb;72(2):63–82. [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. Kaumann A. J., Lobnig B. M. Mode of action of (-)-pindolol on feline and human myocardium. Br J Pharmacol. 1986 Sep;89(1):207–218. doi: 10.1111/j.1476-5381.1986.tb11137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaumann A. J., Sanders L. 5-Hydroxytryptamine causes rate-dependent arrhythmias through 5-HT4 receptors in human atrium: facilitation by chronic beta-adrenoceptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1994 Apr;349(4):331–337. doi: 10.1007/BF00170877. [DOI] [PubMed] [Google Scholar]
  22. Kaumann A. J., Sanders L. Both beta 1- and beta 2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium. Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):536–540. doi: 10.1007/BF00173215. [DOI] [PubMed] [Google Scholar]
  23. Krief S., Lönnqvist F., Raimbault S., Baude B., Van Spronsen A., Arner P., Strosberg A. D., Ricquier D., Emorine L. J. Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest. 1993 Jan;91(1):344–349. doi: 10.1172/JCI116191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Langin D., Portillo M. P., Saulnier-Blache J. S., Lafontan M. Coexistence of three beta-adrenoceptor subtypes in white fat cells of various mammalian species. Eur J Pharmacol. 1991 Jul 9;199(3):291–301. doi: 10.1016/0014-2999(91)90492-9. [DOI] [PubMed] [Google Scholar]
  25. Liggett S. B., Freedman N. J., Schwinn D. A., Lefkowitz R. J. Structural basis for receptor subtype-specific regulation revealed by a chimeric beta 3/beta 2-adrenergic receptor. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3665–3669. doi: 10.1073/pnas.90.8.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lönnqvist F., Krief S., Strosberg A. D., Nyberg S., Emorine L. J., Arner P. Evidence for a functional beta 3-adrenoceptor in man. Br J Pharmacol. 1993 Nov;110(3):929–936. doi: 10.1111/j.1476-5381.1993.tb13902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Man in 't Veld A. J., Schalekamp M. A. Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications. Br Med J (Clin Res Ed) 1981 Mar 21;282(6268):929–931. doi: 10.1136/bmj.282.6268.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nantel F., Bonin H., Emorine L. J., Zilberfarb V., Strosberg A. D., Bouvier M., Marullo S. The human beta 3-adrenergic receptor is resistant to short term agonist-promoted desensitization. Mol Pharmacol. 1993 Apr;43(4):548–555. [PubMed] [Google Scholar]
  29. Nantel F., Bouvier M., Strosberg A. D., Marullo S. Functional effects of long-term activation on human beta 2- and beta 3-adrenoceptor signalling. Br J Pharmacol. 1995 Mar;114(5):1045–1051. doi: 10.1111/j.1476-5381.1995.tb13311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Revelli J. P., Muzzin P., Paoloni A., Moinat M., Giacobino J. P. Expression of the beta 3-adrenergic receptor in human white adipose tissue. J Mol Endocrinol. 1993 Apr;10(2):193–197. doi: 10.1677/jme.0.0100193. [DOI] [PubMed] [Google Scholar]
  31. Sanders L., Lynham J. A., Bond B., del Monte F., Harding S. E., Kaumann A. J. Sensitization of human atrial 5-HT4 receptors by chronic beta-blocker treatment. Circulation. 1995 Nov 1;92(9):2526–2539. doi: 10.1161/01.cir.92.9.2526. [DOI] [PubMed] [Google Scholar]
  32. Thomas R. F., Liggett S. B. Lack of beta 3-adrenergic receptor mRNA expression in adipose and other metabolic tissues in the adult human. Mol Pharmacol. 1993 Mar;43(3):343–348. [PubMed] [Google Scholar]
  33. 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]
  34. Wheeldon N. M., McDevitt D. G., Lipworth B. J. Cardiac effects of the beta 3-adrenoceptor agonist BRL35135 in man. Br J Clin Pharmacol. 1994 Apr;37(4):363–369. doi: 10.1111/j.1365-2125.1994.tb04290.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES