Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Apr;33(4):417–422. doi: 10.1111/j.1365-2125.1992.tb04061.x

The effect of orthotopic transplantation on total, beta 1- and beta 2-adrenoceptors in the human heart.

M R Chester 1, B Madden 1, D Barnett 1, M Yacoub 1
PMCID: PMC1381332  PMID: 1315563

Abstract

1. [125I]-(-)pindolol binding was used to determine beta-adrenoceptor density in homogenate preparations of right ventricular endomyocardial biopsies from 43 non-rejecting patients over the first 13 months following cardiac transplantation. The selective beta 1 subtype antagonist ligand CGP 20712A was used to determine the subtype density in 32 of the patients. Biopsy specimens from 15 donor hearts were used as controls. 2. beta-adrenoceptor density (expressed in terms of fmol mg-1 protein) was increased in the group of transplanted hearts as a whole compared with the donor hearts with respect to total (35 +/- 2 vs 23 +/- 2) and the beta 1 subtype (25 +/- 2 vs 16 +/- 2) whereas the beta 2 subtype and radioligand dissociation constant did not differ. 3. Non-parametric analysis of variance of total receptor density over time revealed significant heterogeneity which appears to be due to a discrete increase in beta-adrenoceptor density during the 4th post operative month. 4. These results indicate that beta-adrenoceptor density is not constant following transplantation. Furthermore, the increase in receptor density following transplantation is due mainly to an increase in the beta 1 subtype without a significant change in the beta 2 subtype.

Full text

PDF
417

Selected References

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

  1. Barovsky K., Brooker G. (-)-[125I]-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells. J Cyclic Nucleotide Res. 1980;6(4):297–307. [PubMed] [Google Scholar]
  2. Bjørnerheim R., Simonsen S., Golf S. Increased beta-adrenoceptor-coupled adenylate cyclase response in transplanted human hearts. Scand J Clin Lab Invest. 1987 Nov;47(7):661–665. [PubMed] [Google Scholar]
  3. Bristow M. R., Ginsburg R., Minobe W., Cubicciotti R. S., Sageman W. S., Lurie K., Billingham M. E., Harrison D. C., Stinson E. B. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982 Jul 22;307(4):205–211. doi: 10.1056/NEJM198207223070401. [DOI] [PubMed] [Google Scholar]
  4. Bristow M. R., Hershberger R. E., Port J. D., Minobe W., Rasmussen R. Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol. 1989 Mar;35(3):295–303. [PubMed] [Google Scholar]
  5. Cook N., Nahorski S. R., Barnett D. B. (-)-[125I]pindolol binding to the human platelet beta-adrenoceptor: characterisation and agonist interactions. Eur J Pharmacol. 1985 Jul 17;113(2):247–254. doi: 10.1016/0014-2999(85)90742-3. [DOI] [PubMed] [Google Scholar]
  6. Denniss A. R., Marsh J. D., Quigg R. J., Gordon J. B., Colucci W. S. Beta-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts. Circulation. 1989 May;79(5):1028–1034. doi: 10.1161/01.cir.79.5.1028. [DOI] [PubMed] [Google Scholar]
  7. Fowler M. B., Laser J. A., Hopkins G. L., Minobe W., Bristow M. R. Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation. 1986 Dec;74(6):1290–1302. doi: 10.1161/01.cir.74.6.1290. [DOI] [PubMed] [Google Scholar]
  8. Gilbert E. M., Eiswirth C. C., Mealey P. C., Larrabee P., Herrick C. M., Bristow M. R. Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin. Circulation. 1989 Feb;79(2):344–349. doi: 10.1161/01.cir.79.2.344. [DOI] [PubMed] [Google Scholar]
  9. Hasking G. J., Esler M. D., Jennings G. L., Burton D., Johns J. A., Korner P. I. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986 Apr;73(4):615–621. doi: 10.1161/01.cir.73.4.615. [DOI] [PubMed] [Google Scholar]
  10. Kowalski M. T., Haworth D., Lu X., Thomson D. S., Barnett D. B. Comparison of the effects of xamoterol and isoprenaline on rat cardiac beta-adrenoceptors: studies of function and regulation. Br J Pharmacol. 1990 Jan;99(1):27–30. doi: 10.1111/j.1476-5381.1990.tb14648.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Lefkowitz R. J. Clinical physiology of adrenergic receptor regulation. Am J Physiol. 1982 Jul;243(1):E43–E47. doi: 10.1152/ajpendo.1982.243.1.E43. [DOI] [PubMed] [Google Scholar]
  13. Lurie K. G., Bristow M. R., Reitz B. A. Increased beta-adrenergic receptor density in an experimental model of cardiac transplantation. J Thorac Cardiovasc Surg. 1983 Aug;86(2):195–201. [PubMed] [Google Scholar]
  14. Maisel A. S., Motulsky H. J., Insel P. A. Life cycles of cardiac alpha 1- and beta-adrenergic receptors. Biochem Pharmacol. 1987 Jan 1;36(1):1–6. doi: 10.1016/0006-2952(87)90375-3. [DOI] [PubMed] [Google Scholar]
  15. Myers M. G., Norris J. W., Hachniski V. C., Sole M. J. Plasma norepinephrine in stroke. Stroke. 1981 Mar-Apr;12(2):200–204. doi: 10.1161/01.str.12.2.200. [DOI] [PubMed] [Google Scholar]
  16. Neve K. A., Molinoff P. B. Effects of chronic administration of agonists and antagonists on the density of beta-adrenergic receptors. Am J Cardiol. 1986 Apr 25;57(12):17F–22F. doi: 10.1016/0002-9149(86)90883-0. [DOI] [PubMed] [Google Scholar]
  17. Nomura Y., Kajiyama H., Segawa T. Hypersensitivity of cardiac beta-adrenergic receptors after neonatal treatment of rats with 6-hydroxydopa. Eur J Pharmacol. 1980 Aug 29;66(2-3):225–232. doi: 10.1016/0014-2999(80)90146-6. [DOI] [PubMed] [Google Scholar]
  18. Norris J. W. Effects of cerebrovascular lesions on the heart. Neurol Clin. 1983 Feb;1(1):87–101. [PubMed] [Google Scholar]
  19. Politi P. M., Rothlin R. P., Pinto J. E. Acute effects of doxorubicin on chronotropic and inotropic mechanisms in guinea pig atria. Cancer Treat Rep. 1985 Jul-Aug;69(7-8):859–865. [PubMed] [Google Scholar]
  20. Robison T. W., Giri S. N. Effects of chronic administration of doxorubicin on myocardial beta-adrenergic receptors. Life Sci. 1986 Aug 25;39(8):731–736. doi: 10.1016/0024-3205(86)90021-4. [DOI] [PubMed] [Google Scholar]
  21. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  22. Strasser R. H., Stiles G. L., Lefkowitz R. J. Translocation and uncoupling of the beta-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo. Endocrinology. 1984 Oct;115(4):1392–1400. doi: 10.1210/endo-115-4-1392. [DOI] [PubMed] [Google Scholar]
  23. Wolfe B. B., Harden T. K., Molinoff P. B. beta-adrenergic receptors in rat liver: effects of adrenalectomy. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1343–1347. doi: 10.1073/pnas.73.4.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yusuf S., Theodoropoulos S., Mathias C. J., Dhalla N., Wittes J., Mitchell A., Yacoub M. Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade. Circulation. 1987 Apr;75(4):696–704. doi: 10.1161/01.cir.75.4.696. [DOI] [PubMed] [Google Scholar]

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

RESOURCES