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. 1971 Aug;68(8):1773–1777. doi: 10.1073/pnas.68.8.1773

A Fraction of the Ventricular Myocardium That Has the Specificity of the Cardiac Beta-Adrenergic Receptor

Robert J Lefkowitz 1,2, Edgar Haber 1,2
PMCID: PMC389290  PMID: 4399664

Abstract

The 78,000 × g microsomal fraction of canine ventricular myocardium effected a 20-fold concentration of [3H]norepinephrine from a 10-9 M solution. The [3H]norepinephrine bound was displaced by physiologic concentrations of the beta-adrenergic catecholamines isoproterenol, epinephrine, and norepinephrine, in that order, which is the order of effectiveness of their actions on the force and rate of cardiac contraction. Alpha-adrenergic compounds did not displace [3H]norepinephrine until concentrations four orders of magnitude greater were reached. The beta-adrenergic blocker propranolol displaced at 10-6 M, whereas the alpha-adrenergic blocker phentolamine was inactive. Metabolites of the catecholamines did not compete for this binding site. It is concluded that, on the basis of specificity and affinity of binding, these microsomal particles are likely to contain the beta-adrenergic receptor.

Keywords: norepinephrine binding, displacement

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Selected References

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

  1. Epstein S. E., Levey G. S., Skelton C. L. Adenyl cyclase and cyclic AMP. Biochemical links in the regulation of myocardial contractility. Circulation. 1971 Mar;43(3):437–450. doi: 10.1161/01.cir.43.3.437. [DOI] [PubMed] [Google Scholar]
  2. GILLIS C. N. CHARACTERISTICS OF NOREPINEPHRINE RETENTION BY A SUBCELLULAR FRACTION OF RABBIT HEART. J Pharmacol Exp Ther. 1964 Oct;146:54–60. [PubMed] [Google Scholar]
  3. KIRSHNER N. Uptake of catecholamines by a particulate fraction of the adrenal medulla. J Biol Chem. 1962 Jul;237:2311–2317. [PubMed] [Google Scholar]
  4. MURAD F., CHI Y. M., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. III. The effect of catecholamines and choline esters on the formation of adenosine 3',5'-phosphate by preparations from cardiac muscle and liver. J Biol Chem. 1962 Apr;237:1233–1238. [PubMed] [Google Scholar]
  5. Michaelson I. A., Taylor P. W., Jr, Richardson K. C., Titus E. Uptake and metabolism of dl-norepinephrine by subcellular particles of rat heart. J Pharmacol Exp Ther. 1968 Apr;160(2):277–291. [PubMed] [Google Scholar]
  6. POTTER L. T., AXELROD J. PROPERTIES OF NOREPINEPHRINE STORAGE PARTICLES OF THE RAT HEART. J Pharmacol Exp Ther. 1963 Dec;142:299–305. [PubMed] [Google Scholar]
  7. Robison G. A., Butcher R. W., Sutherland E. W. Adenyl cyclase as an adrenergic receptor. Ann N Y Acad Sci. 1967 Feb 10;139(3):703–723. doi: 10.1111/j.1749-6632.1967.tb41239.x. [DOI] [PubMed] [Google Scholar]
  8. Talley R. C., Goldberg L. I., Johnson C. E., McNay J. L. A hemodynamic comparison of dopamine and isoproterenol in patients in shock. Circulation. 1969 Mar;39(3):361–378. doi: 10.1161/01.cir.39.3.361. [DOI] [PubMed] [Google Scholar]
  9. Tomasi V., Koretz S., Ray T. K., Dunnick J., Marinetti G. V. Hormone action at the membrane level. II. The binding of epinephrine and glucagon to the rat liver plasma membrane. Biochim Biophys Acta. 1970 Jul 7;211(1):31–42. doi: 10.1016/0005-2736(70)90120-3. [DOI] [PubMed] [Google Scholar]
  10. Von Euler U. S. Some factors affecting catecholamine uptake, storage, and release in adrenergic nerve granules. Circ Res. 1967 Dec;21(6 Suppl):5–11. [PubMed] [Google Scholar]
  11. von Euler U. S., Lishajko F. Effect of directly and indirectly acting sympathomimetic amines on adrenergic transmitter granules. Acta Physiol Scand. 1968 May-Jun;73(1):78–92. doi: 10.1111/j.1748-1716.1968.tb04085.x. [DOI] [PubMed] [Google Scholar]
  12. von Euler U. S., Lishajko F. Inhibitory action of adrenergic blocking agents on reuptake and net uptake of noradrenaline in nerve granules. Acta Physiol Scand. 1968 Nov;74(3):501–506. doi: 10.1111/j.1748-1716.1968.tb04258.x. [DOI] [PubMed] [Google Scholar]

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