Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of digitalis on central sympathetic neurons have been proposed to alter sympathetic influences on the heart and to contribute to the induction of arrhythmias. Recently, however, we have presented evidence which indicates that the involvement of a direct central action of digitalis is negligible in the alteration of sympathetic nerve activity after i.v. administration of the drug. Thus, a group of experiments were designed to determine if central drug concentrations or biochemical events in the brain would suggest a central action of the drug. Tritiated digoxin (20 microng/kg) was injected i.v. into cats every 15 minutes until ventricular fibrillation occurred. The concentrations of digoxin in cerebrospinal fluid and serum increased linearly with time as the cumulative dose of digoxin was increased. At the mean arrhythmic dose, 140 microng/kg, cerebrospinal fluid contained approximately 10 nM digoxin whereas free digoxin concentration in serum was approximately 30 nM and total digoxin concentration in serum was approximately 120 nM. Since inhibition of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) is often associated with the pharmacological effects of digitalis, effects of nanomolar concentrations of digoxin on Na+,K+-ATPase activity were determined in vitro. The concentration of digoxin faund in cerebrospinal fluid at arrhythmia inhibited Na+,K+-ATPase only slightly (5-10%). Activity of Na+,K+-ATP-ase was also examined in brains of cats which had died in ventricular arrhythmias due to treatment with lethal dose of digitoxin. After ventricular fibrillation, the cat brains were removed and Na+,K+-ATPase activity and ouabain binding were determined in eight areas. No reduction in Na+,K+-ATPase activity or [3H]ouabain binding was observed in any area. Thus, it appeared that toxic doses of digitalis did not cause sail to provide evidence for central effects of toxic doses of digoxin or digitoxin.
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PMID:Digitalis toxicity: lack of marked effect on brain na+,k+-adenosine triphosphatase in the cat. 13 66

alpha-Adrenergic blockade with phentolamine or prazosin but not beta-adrenergic blockade reduces premature ventricular complexes and abolished ventricular fibrillation induced by coronary artery ligation or reperfusion in cats. The protective influences were independent of regional coronary flow or systemic hemodynamics. Efferent sympathetic nerve stimulation increased the idioventricular rate (IVR) prior to myocardial ischemia, a response blocked by propranolol, whereas during reperfusion the increased IVR was abolished only by alpha-blockade. Enhanced alpha-adrenergic responsiveness during reperfusion was also apparent with the alpha-agonist methoxamine. More recently we have demonstrated that alpha-adrenergic receptors, assessed by ligand binding with 3H-prazosin, increased nearly twofold in ischemic myocardium by 30 minutes (Bmax = 14 + 2 to 27 + 3 fmol/mg prot) and remain elevated during early reperfusion (12 + 1 to 18 + 1) before returning to control values by 15 minutes after reperfusion. 3H-DHA binding or Na+- -K+ adenosine triphosphatase activity was not altered at any time, indicating the specificity of the alteration. Thus enhanced alpha-adrenergic receptors and suggests the potential use of alpha-adrenergic blockade as one intervention to alleviate these malignant dysrhythmias.
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PMID:Enhanced alpha-adrenergic responsiveness in ischemic myocardium: role of alpha-adrenergic blockade. 611 77

Intractable ventricular tachyarrhythmia associated with hypomagnesemia responds well to magnesium given intravenously. Two patients with recurrent ventricular tachycardia and ventricular fibrillation associated with normal serum magnesium levels and resistant to treatment with potassium chloride, lidocaine and bretylium tosylate responded dramatically to the administration of magnesium sulfate. A third patient in whom the serum magnesium level was unknown also showed dramatic response to magnesium therapy. Magnesium depletion probably interferes with sodium-potassium adenosine triphosphatase enzyme activity and causes ionic imbalance and electrical instability of purkinje's fibers. Without obvious magnesium depletion this element in high concentration may still prolong transient inward current, prolong the effective refractory period, increase the membrane potential and control ventricular tachyarrhythmia. When ventricular fibrillation or malignant ventricular tachycardia cannot be controlled with lidocaine and other conventional drugs, we recommend infusing magnesium sulfate, 2 to 3 grams in one minute, followed by 10 grams over five hours.
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PMID:Magnesium therapy for intractable ventricular tachyarrhythmias in normomagnesemic patients. 661 8