Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of beta-adrenoceptor blockers on mitochondrial ATPase activity in guinea pig heart preparations. 135 92

Atenolol has been shown to be stored and secreted from PC12 cells by calcium-dependent and stereoselective mechanisms. The present study was designed to determine if the cytoplasmic amine storage granule was the site for storage and release of atenolol and if the drug was, in fact, an enantiomeric selective substrate for the vesicular amine transport protein. Uptake of racemic [3H]atenolol and (-)-[3H]norepinephrine was studied in a vesicular preparation of storage granules isolated from PC12 cells. Uptake of both molecules was found to be ATP-dependent (80%) and to reach steady state in approximately 10 to 15 min. Uptake and storage was inhibited (95%) by either reserpine, an inhibitor of the vesicular amine carrier, or by nigericin which dissipates the proton gradient across the membrane. Uptake of neither compound was inhibited by desipramine, an inhibitor of uptake 1, or oligomycin, an inhibitor of mitochondrial adenosine triphosphatase. Furthermore, uptake of the (-)-enantiomer of atenolol was found to be approximately 5-fold greater than the (+)-enantiomer. Kinetic studies revealed a Km of 184 microM for (+/-)-atenolol and 79 microM for (-)-norepinephrine and Vmax values of 750 and 503 pmol/min/mg of protein for atenolol and norepinephrine, respectively. The interaction of the two compounds with the transport process was found to be kinetically competitive. In separate experiments, atenolol was also found to be transported stereoselectively into bovine adrenal chromaffin granule ghosts and to be ATP dependent (85%) and reserpine sensitive (44%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stereoselective uptake of atenolol into storage granules isolated from PC12 cells. 272 36