The effect of propranolol and its analogs on Ca++ transport by sarcoplasmic reticulum vesicles

E Noack, M Kurzmack, S Verjovski-Almeida and G Inesi

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

Volume 206, Issue 2, pp. 281-288, 08/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics