The effect of verapamil on the Ca2+-transporting and Ca2+-ATPase activity of isolated cardiac sarcolemmal preparations
Por:
MAS-OLIVA J., NAYLER W.G.
Publicada:
1 ene 1980
Resumen:
The effect of (±)-, (+)- and (-)-verapamil on the Ca2+-binding, Ca2+ -transporting activity, and Ca2+ -dependent adenosine triphosphatase (ATPase) activity of isolated cardiac sarcolemmal preparations was studied. Enzymatic treatment was used to establish the nature of the sites facilitating [14C]-(±)-verapamil binding. (±)-Verapamil 1 ?M inhibited the passive binding of 45Ca2+. The (+)- and (-)-isomers were equiactive. (±)-Verapamil 1 ?M inhibited the ATP-dependent transport of 45Ca2+ and the associated activation of the Ca2+ - sensitive ATPase. The activity resided in the (-)-isomer. Lineweaver-Burke plots for the initial rates of ATP-dependent transport showed that the inhibition induced by the (-)-isomer was accompanied by a reduced K(m) and V(max). Enzymatic removal of N-acetyl neuraminic acid and galactose redidues increased [14C]-(±)-verapamil binding; removal of N-acetylglucosamine and treatment with phospholipase C and trypsin decreased the binding. These results have been interpreted to mean that (-)-verapamil interferes with the ATP-dependent Ca2+ -transporting properties of the sarcolemma, and that this effect is accompanied by an altered activity of the intrinsic Ca2+ -sensitive ATPase. N-acetylneuraminic acid and galactose residues do not provide binding sites for verapamil at the cell surface.
Filiaciones:
MAS-OLIVA J.:
Department of Cardiac Medicine, Cardiothoracic Institute, University of London, 2 Beaumont Street, London, W1N 2DX, United Kingdom
NAYLER W.G.:
Department of Cardiac Medicine, Cardiothoracic Institute, University of London, 2 Beaumont Street, London, W1N 2DX, United Kingdom
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