Elevation of beta-adrenergic receptor density in human lymphocytes after propranolol administration

J Clin Invest. 1980 May;65(5):949-57. doi: 10.1172/JCI109781.

Abstract

Abrupt withdrawal after the chronic administration of propranolol has resulted in clinical syndromes that suggest adrenergic hypersensitivity. The effect of propranolol administration and withdrawal on beta-adrenergic receptors was studied in human lymphocyte membranes. Receptor density was quantitated by direct binding assays with the radioligand [125I]iodohydroxybenzylpindolol. Administration of propranolol (160 mg/d) for 8 d resulted in trough plasma levels of approximately 35 ng/ml. By day 5 of propranolol administration the density of beta-adrenergic receptors had increased 43 +/- 4% (P less than 0.01) above pretreatment levels. Abrupt withdrawal of propranolol was followed by the disappearance of propranolol from the plasma within 24 h. The density of beta-adrenergic receptors did not return to pretreatment level for several days. Physiologic supersensitivity of beta-adrenergic receptor-mediated responses was suggested by the appearance of significant increases in the orthostatic change in heart rate (P less than 0.05) and the orthostatic change in the heart rate-systolic blood pressure product (P less than 0.01) during the first 48 h after propranolol withdrawal. These data show that propranolol administration leads to an increase in the density of beta-adrenergic receptors in human tissue. The results are consistent with the hypothesis that some of the untoward effects observed after abrupt discontinuation of propranolol are caused by beta-receptor-mediated adrenergic hypersensitivity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / blood
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Blood Pressure / drug effects
  • Female
  • Heart Rate / drug effects
  • Humans
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Male
  • Phentolamine / pharmacology
  • Pindolol / analogs & derivatives
  • Pindolol / blood
  • Pindolol / pharmacology
  • Propranolol / blood
  • Propranolol / pharmacology*
  • Receptors, Adrenergic / drug effects*
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / metabolism
  • Substance Withdrawal Syndrome / blood*
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta
  • iodohydroxybenzylpindolol
  • Propranolol
  • Pindolol
  • Phentolamine