Differential effect of r-56865 on ouabain binding to isolated sarcolemma and intact atrial tissue of guinea-pigHEERS, 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 journal › Article › Academic › peer-review
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.
|Number of pages||4|
|Journal||British Journal of Pharmacology|
|Publication status||Published - Mar-1991|
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