EFFECT OF PROPRANOLOL AND ITS ANALOGS ON CA++ TRANSPORT BY SARCOPLASMIC-RETICULUM VESICLES

Abstract

Vesicular fragments of cat sarcoplasmic reticulum were used as a model system to investigate the mechanism of propranolol inhibition on various steps of the Ca2+ transport cycle. Ca2+-dependent transfer of ATP terminal phosphate to the sarcoplasmic reticulum protein and formation of the phosphorylated enzyme intermediate were not inhibited by propranolol concentrations effective on Ca2+ transport. Rather, a specific step following enzyme phosphorylation and corresponding to Ca2+ translocation across the membrane was primarily inhibited. The consequent hydrolysis of phosphorylated enzyme is then secondarily inhibited, while Ca2+ independent ATP hydrolysis remained unchanged. Comparison of the relative potencies of several propranolol analogs yielded similar patterns for Ca2+ transport inhibition in sarcomplasmic reticulum vesicles and negative inotropic effects on cardiac muscle. These patterns were at variant with those displayed by these agents with respect to .beta.-adrenergic blockade. Cat tissues were used in this study.