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

2,6-diisopropylphenol (propofol), a general intravenous anesthetic, inhibits the glutamate-dependent Ca2+ entry in rat synaptosomes with an approximate IC50 of 3.0 x 10(-5) M. Propofol, at concentrations above 10(-6) M, also inhibits the ATP-dependent uptake of glutamate in the presence of Ca2+, with an approximate IC50 of 3.5 x 10(-5) M, while it only has a slight inhibitory effect on the release of glutamate. The ouabain-insensitive synaptosomal ATPase is strongly inhibited by propofol, with an IC50 of about 2.5 x 10(-6) M, at concentrations which do not affect the luciferase system.
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PMID:2,6-diisopropylphenol, a general anesthetic, inhibits glutamate action on rat synaptosomes. 168 36

1. We have investigated the effect of propofol, an intravenous anaesthetic, on the intracellular calcium concentration ([Ca2+]i), Ca2+ entry pathways and on inositol phosphate formation in vascular smooth muscle cells. [Ca2+]i and Ca2+ flux were monitored with the Ca(2+)-sensitive fluorescent dye, fura-2, and by 45Ca2+ uptake. Production of labelled inositol phosphates was analysed by anion-exchange chromatography. 2. Treatment of the cells with endothelin-1 (ET-1) increased formation of inositol phosphates and elevated [Ca2+]i due to both release of Ca2+ from intracellular pools and prolonged entry of Ca2+ from outside the cell. Propofol reduced production of inositol phosphates mediated by ET-1 and arginine vasopressin which activate phospholipase C. 3. The sustained Ca2+ entry stimulated by ET-1 was found to occur through the activation of L-type Ca channels. This was inhibited by propofol in a dose-dependent manner. 4. Activation of protein kinase C (PKC) by phorbol esters activated a pharmacologically-similar channel and produced a similar change in [Ca2+]i due to Ca2+ entry. The entry was blocked by an L-type channel antagonist, nicardipine and by the anaesthetic drug, propofol. 5. Treatment of the cells with thapsigargin, a selective inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, also elevated [Ca2+]i by inducing the release of intracellular Ca2+ and the continued entry of extracellular Ca2+ through a nicardipine-insensitive Ca channel. Neither release nor entry induced by thapsigargin was affected by propofol. 6. These findings suggest that propofol selectively inhibits Ca2+ entry through the L-type channel induced by ET-1 and phorbol esters but has no effects on Ca2+ entry via the nicardipine-insensitive channel and on Ca2+ release from intracellular pools initiated by thapsigargin. This may represent one of the mechanisms responsible for propofol-induced vasodilatation.
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PMID:Propofol regulation of calcium entry pathways in cultured A10 and rat aortic smooth muscle cells. 882 36

We determined the direct effects of propofol on the contractility of human nonfailing atrial and failing atrial and ventricular muscles. Atrial and ventricular trabecular muscles were obtained from the failing human hearts of transplant patients or from nonfailing hearts of patients undergoing coronary artery bypass surgery. Isometric contraction variables were recorded before and after propofol was added to the bath in concentrations between 0.056 and 560 microM. The effects of propofol were compared with its commercial vehicle intralipid. To test beta-adrenergic effects in the presence of propofol, 1 microM isoproterenol was added at the end of each experiment. To determine the cellular mechanisms responsible for the actions of propofol, we examined its effects on actomyosin ATPase activity and sarcoplasmic reticulum (SR) Ca(2+) uptake in nonfailing atrial tissues. Propofol caused a concentration-dependent decrease in maximal developed tension in all muscles, which became significant (P < 0.05) at concentrations exceeding the clinical range (> or =56 microM). Isoproterenol restored contractility to the level achieved before exposure to propofol (P > 0.05 compared with baseline). Failing ventricular muscle exposed to propofol exhibited somewhat diminished ability to recover contractility in response to isoproterenol (P < 0.05 versus failing muscle exposed to intralipid only). Propofol induced a concentration-dependent decrease in the uptake of Ca(2+) into SR vesicles. At the same time, in the presence of 56 microM propofol, the Ca(2+)-activated actomyosin ATPase activity was shifted leftward, demonstrating an increase in myofilament sensitivity to Ca(2+). We conclude that propofol exerts a direct negative inotropic effect in nonfailing and failing human myocardium, but only at concentrations larger than typical clinical concentrations. Negative inotropic effects are reversible with beta-adrenergic stimulation. The negative inotropic effect of propofol is at least partially mediated by decreased Ca(2+) uptake into the SR; however, the net effect of propofol on contractility is insignificant at clinical concentrations because of a simultaneous increase in the sensitivity of the myofilaments to activator Ca(2+).
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PMID:The effects of propofol on the contractility of failing and nonfailing human heart muscles. 1152 17