Document Detail

Antagonism by potassium of the inhibition of (Na(+)+K+) ATPase produced by an endogenous digitalis-like compound extracted from mammalian heart.
MedLine Citation:
PMID:  1339224     Owner:  NLM     Status:  MEDLINE    
The antagonism by potassium of (Na(+)+K+)ATPase inhibition was analyzed in order to further study the presence of endogenous digitalis-like activity in mammalian heart. Digoxin and a partially purified extract prepared from guinea pig cardiac tissue inhibited (Na(+)+K+)ATPase, also obtained from guinea pig heart, in a dose-dependent manner in agreement with Michaelis-Menten kinetics. The effects of both inhibitors were antagonized by increasing the KCl concentration from 0.5 to 5 mM. Hunter-Downs plots were linear, suggesting that the interaction between (Na(+)+K+)ATPase and either digoxin or the extract could be considered as competitive. Ks estimated for KCl from these plots was similar to the K0.5 value obtained by activating the enzyme with KCl, and thus suggesting that both inhibitors, digoxin and the extract, were acting on (Na(+)+K+)ATPase. Digoxin and the extract were able to inhibit [3H]ouabain specific binding to the enzyme in a dose-dependent manner in agreement with a competitive interaction. Ki values estimated from binding experiments were similar to those calculated from Hunter-Downs plots. Data strongly suggest the presence in guinea pig heart of an endogenous compound which is able to inhibit (Na(+)+K+)ATPase solely by binding to the digitalis receptors.
G Castañeda-Hernández; F J Flores-Murrieta
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of medical research     Volume:  23     ISSN:  0188-4409     ISO Abbreviation:  Arch. Med. Res.     Publication Date:  1992  
Date Detail:
Created Date:  1993-10-18     Completed Date:  1993-10-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9312706     Medline TA:  Arch Med Res     Country:  MEXICO    
Other Details:
Languages:  eng     Pagination:  13-7     Citation Subset:  IM    
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., México, D.F.
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MeSH Terms
Cardiotonic Agents / antagonists & inhibitors*,  isolation & purification,  pharmacology
Digoxin / pharmacology
Drug Interactions
Enzyme Activation
Guinea Pigs
Muscle Proteins / antagonists & inhibitors*
Myocardium / chemistry*,  enzymology
Ouabain / metabolism,  pharmacology
Potassium Chloride / pharmacology*
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors,  drug effects*,  metabolism
Tissue Extracts
Reg. No./Substance:
0/Cardiotonic Agents; 0/Muscle Proteins; 0/Tissue Extracts; 20830-75-5/Digoxin; 630-60-4/Ouabain; 7447-40-7/Potassium Chloride; EC ATPase

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