Effects of beta-adrenoceptor blockers on mitochondrial ATPase activity in guinea pig heart preparations.
The effects of three beta-adrenoceptor blockers atenolol, indenolol and nadolol on myocardial mitochondrial ATPase (ATP: phosphohydrolase EC 3.6.1.3) activity were evaluated and compared with that of propranolol in guinea pig heart preparations. Propranolol and indenolol inhibited ATPase activity with IC50 values of 4.4 +/- 0.5 and 5.3 +/- 0.4 mM, respectively. In contrast, however, nadolol and atenolol markedly enhanced mitochondrial ATPase activity. Atenolol increased the enzyme activity by approximately 5, 240 and 950%, while nadolol enhanced it by 13, 280 and 2800% at 100 microM, 1.0 mM and 10.0 mM, respectively. The results indicate that these drugs exhibit two modes of interaction with the mitochondrial ATPase: inhibition by propranolol and indenolol and stimulation by atenolol and nadolol. The inhibitory actions are probably related to the membrane-stabilizing effects and therefore antiarrhythmic actions of the two drugs, while the stimulatory effects of atenolol and nadolol are probably a result of interactions with some component of oxidative phosphorylation or the respiratory chain.
Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
A A
AA
Almotrefi
N
N
Dzimiri
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007192:Indenes / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D009248:Nadolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D007192:Indenes; D011412:Propanolamines; D009248:Nadolol; D001262:Atenolol; C002989:indenolol; D000251:Adenosine Triphosphatases