Propranolol-induced inhibition of cardiac microsomal calcium-uptake, calcium-binding, and epinephrine-stimulated adenylate cyclase

Abstract

Both cardiac microsomal Ca-binding and Ca-uptake were inhibited by propranolol. Both 1-propranolol (which has β-blocking and local anaesthetic actions) and d-propranolol (which lacks the former action) inhibited Ca-binding and Ca-uptake; sensitivity to the 1-isomer being slightly greater than that to the d-isomer. Inhibition of Ca-binding by propranolol could be reversed by Ca2+; kinetic analysis indicated the existence of competitive inhibition between Ca2+ and the drug. Inhibition of Ca-uptake by propranolol was also partially reversed by Ca2+, although kinetic analysis to define competition could not be carried out because Ca-uptake in the range of Ca2+ concentration < 3 x 106 M does not exhibit saturation kinetics. Isoproterenol in concentrations equal to or greater than those of propranolol did not reverse inhibition of either Ca-binding or Ca-uptake. Cardiac microsomal adenylate cyclase was not inhibited by concentrations of d,l-propranolol that inhibit Ca-binding and Ca-uptake but the stimulation of adenylate cyclase by 104 M epinephrine was abolished by an equimolar concentration of d,l-propranolol. Inhibition of cardiac microsomal Ca-binding and Ca-uptake cannot, therefore, be attributed to a direct β-blocking action of propranolol upon calcium transport by the sarcoplasmic reticulum.