Mechanism of inhibition of sodium- and potassium-dependent adenosine triphosphatase by the isoquinoline derivative BIIA: a specific interaction with sodium activation
| Autor: | Kurt Greeff, Alanna A.L. Fox |
|---|---|
| Rok vydání: | 1981 |
| Předmět: |
Stereochemistry
Hydrochloride Sodium Potassium ATPase Guinea Pigs chemistry.chemical_element Biochemistry chemistry.chemical_compound Adenosine Triphosphate Animals Drug Interactions Magnesium Na+/K+-ATPase Isoquinoline Ouabain Pharmacology chemistry.chemical_classification biology Dose-Response Relationship Drug Substrate (chemistry) Hydrogen-Ion Concentration Isoquinolines Kinetics Enzyme chemistry biology.protein Sodium-Potassium-Exchanging ATPase |
| Zdroj: | Biochemical pharmacology. 30(6) |
| ISSN: | 0006-2952 |
| Popis: | An isoquinoline derivative, 3-benzylamino-5,6-dihydro-8,9-dimethoxy-imidazo-(5,1-a)-iso-quinoline hydrochloride, BIIA, with positive inotropic and antiarrhythmic actions, reversibly inhibited the Na + , K + -ATPase of deoxycholate and NaI treated musomes from guinea-pig heart, brain and kidney. The inhibition was pH dependent, increasing with increasing pH and the concentration of the highly lipid soluble, unprotonated molecule. BIIA inhibited Na + , K + -ATPase in a concentration range of 1–100 μmoles/l, in a manner uncompetitive with respect to ATP and K + , and competitive with respect to Na + , K + PNPPase of the same preparation was also inhibited by BIIA, albeit at higher concentrations. This inhibition was competitive with K + . Affinity for substrate, as measured with [ 14 C]-ATP, was increased and labelling from AT 32 P decreased competitive with Na + . BIIA decreases the affinity of the enzyme for (Mg 2+ + P i ) supported ouabain binding, higher concentrations of BIIA also affect (Na + ATP) supported binding. It is suggested that BIIA enters a hydrophobic environment of the Na + , K + -ATPase and interacts at or near the Na + -activation sites, inhibiting the formation of the phosphorylated intermediate. |
| Databáze: | OpenAIRE |
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