Exaprolol as a modulator of heart sarcolemmal (Na+ + K+)-ATPase. Evidence for interaction with an essential sulfhydryl group in the catalytic centre of the enzyme

Gen Physiol Biophys. 1985 Jun;4(3):257-64.

Abstract

Beta-adrenoceptor blocking agents may have, in addition to their primary action, also ancillary effects on the cell membrane. In the present paper the non-specific interaction of exaprolol with the ATPase systems in isolated rat heart sarcolemmal membranes was investigated. When preincubated with sarcolemmal membranes in vitro, exaprolol in concentrations below 10(-4) mol.l-1 had no significant effect on sarcolemmal Mg2+-, Ca2+- and (Na+ + K+)-ATPase activities. At exaprolol concentration of 10(-4) mol.l-1 the Mg2+- and Ca2+-ATPase activities became inhibited whereas the (Na+ + K+)-ATPase activity was markedly stimulated. A kinetic analysis of these interactions revealed a non-competitive inhibition of Mg2+- and Ca2+-ATPase. In the case of (Na+ + K+)-ATPase a synergistic type of stimulation characterized by an exaprolol-induced conversion of an essential sulfhydryl group in the active site of the enzyme to the more reactive [S-] form has been observed thus increasing the affinity of the enzyme to ATP. Exaprolol concentrations exceeding 5 X 10(-4) mol.l-1 induced an overall depression of the investigated enzyme activities.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Binding Sites
  • Ca(2+) Mg(2+)-ATPase
  • Calcium-Transporting ATPases / metabolism
  • Heart / drug effects*
  • Myocardium / enzymology*
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Sarcolemma / drug effects
  • Sarcolemma / enzymology*
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Sulfhydryl Compounds / metabolism

Substances

  • Adrenergic beta-Antagonists
  • Propanolamines
  • Sulfhydryl Compounds
  • Adenosine Triphosphatases
  • Ca(2+) Mg(2+)-ATPase
  • Calcium-Transporting ATPases
  • Sodium-Potassium-Exchanging ATPase
  • exaprolol