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Differential effect of r-56865 on ouabain binding to isolated sarcolemma and intact atrial tissue of guinea-pig

HEERS, C., SCHEUFLER, E., WILHELM, D., WERMELSKIRCHEN, D., WILFFERT, B. & Peters, T., Mar-1991, In : British Journal of Pharmacology. 102, 3, p. 675-678 4 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • C HEERS
  • E SCHEUFLER
  • D WILHELM
  • D WERMELSKIRCHEN
  • B WILFFERT
  • Thies Peters

1 R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl-2-benzolamine) is a compound known to antagonize cardiac glycoside intoxication. Therefore, the effect of the compound on ouabain binding to intact cardiac tissue as well as cardiac membrane preparations was investigated.

2 The binding of ouabain to highly purified sarcolemmal membranes was not influenced by R 56865 1 x 10(-6) moll-1 (ouabain: K(D) = 1.3 x 10(-7) moll-1, B(max) = 160 pmol mg-1; ouabain + R 56865: K(D) = 1.4 x 10(-7) moll-1, B(max) = 168 pmol mg-1).

3 In contrast to the results in purified membranes, the binding of ouabain (10(-8) moll-1 to 5 x 10(-7) moll-1) to intact atria was significantly reduced.

4 Ouabain, 5 x 10(-7) moll-1, led to a transient positive inotropic effect of about 220% followed by a developing negative inotropic effect after 3 h. R 56865, 10(-7) moll-1, led to a maximal positive inotropic effect of about 290% also followed by a delayed decline of contractile force. A tenfold higher concentration of R 56865 led to sustained positive inotropic effect of about 250% in the same time interval.

5 The different effects of R 56865 on ouabain binding in subcellular preparations and intact tissue do not support the view that R 56865 interferes directly with the action of ouabain on Na/K-ATPase. An indirect effect, which may be mediated by a lowered intracellular sodium load is discussed.

Original languageEnglish
Pages (from-to)675-678
Number of pages4
JournalBritish Journal of Pharmacology
Volume102
Issue number3
Publication statusPublished - Mar-1991

    Keywords

  • INCREASED SODIUM INFLUX, HEART, MUSCLE, TRIPHOSPHATASE, COOPERATIVITY, DEPENDENCE, MYOCARDIUM, PUMP

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