The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin
Por:
Lamers J.M.J., Verdouw P.D., Mas-Oliva J.
Publicada:
1 ene 1996
Resumen:
The Ca2+ channel blockers felodipine and bepridil are known to affect selectively functions of calmodulin. We studied their effects on calmodulin binding and ATPase activities of calmodulin-containing and calmodulin-depleted rabbit heart sarcolemma. Both drugs as well as the specific anti-calmodulin drug calmidazolium at a concentration of 50 ?M, inhibited the Ca2+-stimulated calmodulin binding to calmodulin-depleted sarcolemma. Within the concentration range of 3 to 100 ?M all three drugs also progressively inhibited Ca2+ pumping ATPase in calmodulin containing sarcolemma, although the enzyme was assayed at saturating Ca2+ (100 ?M). The inhibitory potency of calmidazolium and bepridil, but not that of felodipine, increased when the membrane protein concentration in the ATPase assay was lowered. At low membrane protein concentration 30 ?M calmidazolium completely blocked calmodulin-dependent Ca2+ pumping ATPase, whereas the inhibition caused by 30 ?M felodipine or bepridil remained partially. A similar inhibition pattern of the drugs was found in the calmodulin binding experiments. Within a concentration range of 3 to 30 ?M, all three drugs had negligible effects on the basal Ca2+ pumping ATPase which was measured in calmodulin-depleted sarcolemma. In conclusion, the characteristics of the anti-calmodulin action of felodipine on the rabbit heart sarcolemmal Ca2+ pumping ATPase are not different from those of bepridil. Both drugs may inhibit the enzyme by interference with the Ca2+-stimulated binding of calmodulin. © 1987 Martinus Nijhoff Publishers.
Filiaciones:
Lamers J.M.J.:
Department of Biochemistry I, Erasmus University Rotterdam, 3000 DR, Rotterdam, Netherlands
Verdouw P.D.:
Department of Thoraxcenter, Erasmus University Rotterdam, 3000 DR, Rotterdam, Netherlands
Mas-Oliva J.:
Instituta de Fisiologia Celular, Universidad Nacional de Mexico, Mexico 04510, AP70-600, D.F., Mexico
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