TY - JOUR
T1 - Influence of cationic amphiphilic drugs on the characteristics of ouabain-binding to cardiac Na+/K+-ATPase
AU - Dunst, Jürgen
AU - Lüllmann, Heinz
AU - Mohr, Klaus
N1 - Funding Information:
Acknowledgements-This work was supported by the DeutscheF orschungsgemeinschawftit h grant Lu 31/25-3. The skilful technicala ssistanceo f Miss Heike Wilhelm is gratefullya cknowledged.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1983/5/15
Y1 - 1983/5/15
N2 - The influence of 12 cationic amphiphilic compounds on the equilibrium and kinetic characteristics of the binding of tritium-labelled ouabain to the lipoprotein Na+/K+-ATPase present in a crude membrane suspension of guinea pig myocardium was investigated. The drugs, e.g. local anaesthetic, antiarrhythmic and psychotropic agents, inhibited specific binding of ouabain in a concentration-dependent manner by reducing its affinity without affecting the number of binding sites. In the presence of chlorpromazine, propranolol and dibucaine, the decreased affinity of ouabain was due to both a diminished association rate and an increased dissociation rate, while in the presence of the weakly potent procaine only the association rate of ouabain was found to be reduced. The different potency of the catamphiphilic drugs was well correlated to the degree of their hydrophobicity. Evidence is presented that the protonized form of the drugs is the effective one. Concerning the mode of action, the catamphiphilic drugs are proposed to interact with the phospholipid part of the lipoprotein Na+/K+-ATPase, thereby indirectly altering the conformation of the embedded protein moiety and thus reducing the proper fit between ouabain and its receptor.
AB - The influence of 12 cationic amphiphilic compounds on the equilibrium and kinetic characteristics of the binding of tritium-labelled ouabain to the lipoprotein Na+/K+-ATPase present in a crude membrane suspension of guinea pig myocardium was investigated. The drugs, e.g. local anaesthetic, antiarrhythmic and psychotropic agents, inhibited specific binding of ouabain in a concentration-dependent manner by reducing its affinity without affecting the number of binding sites. In the presence of chlorpromazine, propranolol and dibucaine, the decreased affinity of ouabain was due to both a diminished association rate and an increased dissociation rate, while in the presence of the weakly potent procaine only the association rate of ouabain was found to be reduced. The different potency of the catamphiphilic drugs was well correlated to the degree of their hydrophobicity. Evidence is presented that the protonized form of the drugs is the effective one. Concerning the mode of action, the catamphiphilic drugs are proposed to interact with the phospholipid part of the lipoprotein Na+/K+-ATPase, thereby indirectly altering the conformation of the embedded protein moiety and thus reducing the proper fit between ouabain and its receptor.
UR - http://www.scopus.com/inward/record.url?scp=0020584080&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(83)90333-7
DO - 10.1016/0006-2952(83)90333-7
M3 - Journal articles
C2 - 6305363
AN - SCOPUS:0020584080
SN - 0006-2952
VL - 32
SP - 1595
EP - 1600
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 10
ER -
