Effects of beta-adrenergic blockers on Na(+)-K(+)-ATPase activity in guinea-pig heart preparations: comparison with ouabain.
The effects of the beta-adrenergic receptor antagonists carazolol, celiprolol, indenolol and propranolol on myocardial Mg(2+)-dependent, Na(+)- and K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase, EC 3.6.1.3) were compared with those of ouabain in guinea-pig heart preparations. All four drugs inhibited the enzyme activity in a concentration-dependent fashion similar to that shown by ouabain. Celiprolol exerted inhibitory actions (5-95%) in the concentration range of 0.5-3000 microM, while propranolol showed similar activity in the range of 100-4000 microM. Carazolol and indenolol exhibited intermediary effects. Their inhibitory effective ranges were 95-4000 and 10-5000 microM, respectively. The concentrations for half maximal inhibition of the enzyme activity were 0.74 +/- 0.12 mM for carazolol, 0.62 +/- 0.09 mM for celiprolol, 0.80 +/- 0.11 mM for indenolol and 1.03 +/- 0.19 mM for propranolol. Accordingly, the rank order of their potencies exhibited the following trend: celiprolol greater than carazolol greater than indenolol greater than propranolol. The present results show that these drugs exhibit inhibitory actions on the Na(+)-K(+)-ATPase activity, which may be suggested as a possible biochemical basis for their proarrhythmic effects.
Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
A A
AA
Almotrefi
N
N
Dzimiri
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D010042:Ouabain / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D010042:Ouabain; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase