EFFECTS OF PROPRANOLOL AND ITS OPTICAL ISOMERS ON THE RADIOCALCIUM UPTAKE AND THE ADENOSINE TRIPHOSPHATASES OF SKELETAL AND CARDIAC SARCOPLASMIC RETICULUM FRACTIONS (SRF)

¹ Imperial Chemical Industries Ltd., Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, England

The effects of the beta adrenergic blocking drugs, propranolol, pronethalol, MJ-1999 and N-isopropyl-p-nitrophenylethanolamine (INPEA), on the Ca⁺⁺ uptake and the adenosine triphosphatases (ATPases) of skeletal and cardiac sarcoplasmic reticulum fractions (SRF) have been investigated. All produced an inhibition of the Ca⁺⁺ uptake of skeletal and cardiac SRF. The degree of inhibition at any one concentration decreased in the order: (±)-propranolol and its isomers, (±)-pronethalol, INPEA and MJ-1999. With the exception of the dextro isomer of propranolol, this order correlates approximately with their ability to antagonize the ventricular arrhythmias and the chronotropic and inotropic responses of cardiac muscle produced by catecholamines. The ability of these beta adrenergic blocking agents to inhibit cyclic 3', 5'-adenosine monophosphate (3', 5'-AMP)-stimulated glycogenolysis and lipolysis may be related to their modification of Ca⁺⁺ transport across the membranes.

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