title: Differential effects of amiodarone and propranolol on lipid dynamics and enzymatic activities in cardiac sarcolemmal membranes.
abstract: 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 microM by propranolol which inhibited Mg2+ ATPase and increased fluidity above 20 microM. Amiodarone affected all the enzyme activities (except Na+/K+ ATPase): isoproterenol-stimulated adenylate (IC50 = 30 microM), Mg2+ ATPase (IC50 = 20 microM) and K+-stimulated-p-nitrophenylphosphatase were inhibited; 5'nucleotidase was activated above 2 microM. By contrast with propranolol, amiodarone decreased lipid mobility. The effect was linear with the concentration of the drug above 1 microM.
authors.affiliation: SANOFI, Centre de Recherche Labaz-Sanofi, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Chatelain
authors.forename: R
authors.initials: R
authors.lastname: Laruel
authors.forename: P
authors.initials: P
authors.lastname: Vic
authors.forename: R
authors.initials: R
authors.lastname: Brotelle
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009708:Nucleotidases / Q000378:metabolism; D010869:Pindolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D011433:Propranolol; D010869:Pindolol; D009708:Nucleotidases; D009597:4-Nitrophenylphosphatase; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D000638:Amiodarone