Effect of Propranolol on the Erythrocyte Membrane and Mechanism of its Action on the Oxygen Affinity

摘要

Propranolol, a β-adrenergic blocker, is known to decrease the hemoglobin oxygen affinity in concentrations 5 to 10 fold the therapeutic level. Since both intraery-throcytic pH and potassium concentration decrease upon propranololtreatment, the change in oxygen affinity could be based on the Bohr-effect or alternatively due to an increased binding of 2,3-diphosphoglycerate to hemoglobin, secondary to a decrease in intracellular ion-concentration. Using a new method to monitor rapid and small changes in oxygen affinity of intact red blood cells, it is shown that almost the whole effect of propranolol in decreasing the oxygen affinity is attributable to a decrease in intracellular pH. Further, propranolol, a membrane active drug modifies the disc shape of erythrocytes (cupping). This morphological change is not associated with the propranolol induced potassium loss and therefore not a result of the concomittantly occurring loss of cell volume. Depletion of the red cells ATP by incubation with iodoacetate inhibits the effects of propranolol, indicating its possible interference with membrane phosphorylation.