The amphiphilic cationic cardioactive drugs (pindolol, propranolol and amiodarone) were tested for their effects on lipid dynamics (measured by fluorescence depolarization) and on enzymatic activities up to 1 mM in purified cardiac sarcolemmal vesicles from adult rat. The vesicles were enriched 12- to 37-fold (with respect to tissue homogenate) in Na+/K+ATPase, K+-stimulated p-nitrophenylphosphatase, 5'nucleotidase and adenylate cyclase, all of which are believed to be components of sarcolemma. Phospholipids and cholesterol content were enriched 5- and 13-fold respectively. There was very little contamination of the sarcolemmal vesicles by sarcoplasmic reticulum (as judged by Ca2+ATPase and glucose-6-phosphatase activities) or mitochondria (as judged by cytochrome-c-oxidase activity). Pindolol had no effect on lipid dynamics and enzyme activities except for the isoproterenol-stimulated adenylate cyclase. The latter was also totally inhibited at 1 μM by propranolol which inhibited Mg2+ATPase and increased fluidity above 20 μM. Amiodarone affected all the enzyme activities (except Na+/K+ATPase): isoproterenol-stimulated adenylate (IC50= 30 μM), Mg2+ATPase (ic50= 20 μM) and K+-stimulated-p-nitrophenylphosphatase were inhibited; 5'nucleotidase was activated above 2 μM. By contrast with propranolol, amiodarone decreased lipid mobility. The effect was linear with the concentration of the drug above 1 μM. © 1989.
Chatelain, P., Laruel, R., Vic, P., & Brotelle, R. (1989). Differential effects of amiodarone and propranolol on lipid dynamics and enzymatic activities in cardiac sarcolemmal membranes. Biochemical Pharmacology, 38(8), 1231–1239. https://doi.org/10.1016/0006-2952(89)90328-6