Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

12(R)-hydroxyeicosatetraenoic acid (12(R)HETE) is an endogenous corneal epithelial arachidonic acid metabolite formed by the cytochrome P450 system and a potent inhibitor of Na(+)-K(+)-ATPase activity. We studied the effect of topically applied 12(R)HETE, either derived endogenously from corneal epithelium or synthetically prepared, on the IOP of the rabbit eye and compared it to its stereoisomer 12(S)HETE. Topical application of 1 microgram of biologically derived 12(R)HETE to both eyes of rabbits resulted in a marked reduction in IOP: a reduction of 4-7 mmHg occurred within 30-120 min. The IOP reduction effect of a single application of 12(R)HETE was long-lasting (9 days), whereas no effect on IOP was found for the vehicle control. Using synthetic compound, we demonstrated that the effect of 12(R)HETE on IOP is dose-dependent. Single topical application of 1, 10, and 50 micrograms of 12(R)HETE caused a reduction in IOP of 4, 6, and 12 mmHg, respectively. The stereoisomer, 12(S)HETE, did not have any effect on IOP at doses up to 5 micrograms. The IOP reduction effect of 12(R)HETE was not associated with hyperemia, appearance of flare, miotic response, or increased protein concentration of the aqueous humor. This study was the first to demonstrate that an endogenous inhibitor of Na(+)-K(+)-ATPase generated by the corneal epithelium potently and specifically lowers IOP in rabbits. Further studies are needed to elucidate the mechanism by which 12(R)HETE lowers IOP.
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PMID:12(R)-hydroxyeicosatetraenoic acid, an endogenous corneal arachidonate metabolite, lowers intraocular pressure in rabbits. 231 92

Adrenaline markedly increased the ouabain-sensitive 22Na+-efflux by stimulating the Na+-K+ pump in frog skeletal muscle. The facilitatory effects of adrenaline had the following properties. The effects of adrenaline on the ouabain-sensitive Na+-efflux were observed at concentrations greater than 0.1 microM and the magnitude increased with concentration up to 10 microM. At a concentration of 30 microM, adrenaline markedly augmented the ouabain-sensitive Na+-efflux, but other biogenic amines were less effective (noradrenaline and dopamine) or ineffective (histamine and serotonin). The increase of Na+-efflux induced by 1 microM adrenaline was blocked by 3 microM propranolol, but not by 3 microM phenoxybenzamine. The properties of the facilitatory action of adrenaline on the ouabain-sensitive Na+-efflux suggest that beta-adrenoceptors have an important role in modulating the Na+-K+ pump activity in the skeletal muscle membrane. The protein complex localized in excitable membranes, namely the Na+-K+ ATPase-beta-adrenoceptor complex, may be the functional unit which operates the membrane machinery driving the Na+-K+ pump.
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PMID:Beta-adrenergic modulation of the Na+-K+ pump in frog skeletal muscles. 241 22

Epinephrine-induced hypokalemia appears to be mediated by beta 2-agonist activation of Na+/K+ ATPase. To determine whether dopamine and dobutamine induce hypokalemia, eight adult mongrel dogs were anesthetized and studied in random crossover fashion. Potassium [K+] was measured with an ion-selective microelectrode, and central hemodynamics were measured continuously. After stabilization, dopamine and dobutamine were infused at doses of 2, 4, 8, and 20 micrograms/kg/min (15-min increments/dose), and 0.9% NaCl was infused at equivalent volumes, with a 1-h washout between treatments. The mean change in [K+] at each infusion rate was compared between treatments among dogs with an adequate hemodynamic response. Among dopamine responders (n = 5), [K+] decreased from 3.74 +/- 0.42 mEq/L at baseline to 3.63 +/- 0.51 at 2 micrograms/kg/min (p less than 0.02) and was not significantly different at higher doses. Among dobutamine responders (n = 7), [K+] decreased from 3.52 +/- 0.74 at baseline to 3.31 +/- 0.87 at 8 micrograms/kg/min (p less than 0.02) and 3.25 +/- 0.86 at 20 micrograms/kg/min (p less than 0.02), and was not significantly different at lower doses. We conclude that dopamine and dobutamine induce significant hypokalemia, consistent with their adrenergic agonist activity, and this may be related to the known arrhythmogenicity of these agents.
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PMID:Dopamine and dobutamine induce hypokalemia in anesthetized dogs. 247 Oct 6

This study was designed to investigate beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease (ESRD). Plasma potassium was measured over a period of 3 months in 20 patients with ESRD who were receiving the nonselective beta-blocker propranolol (n = 10) or not (n = 10). Both groups were virtually anuric and had a comparable plasma BUN, plasma bicarbonate, and red cell Na-K-ATPase activity. Plasma potassium measured before dialysis was higher in propranolol users than in nonusers (5.6 +/- 0.2 and 4.6 +/- 0.1 mEq/l, p less than 0.005). To examine beta-adrenergic-mediated internal potassium disposal more directly, epinephrine and epinephrine plus propranolol were acutely administered to another group of patients with ESRD and to normal subjects. Epinephrine resulted in a similar fall in plasma potassium in both groups (0.69 +/- 0.20 and 0.63 +/- 0.07 mEq/l, respectively), thereby suggesting unimpaired beta-adrenergic-mediated extrarenal potassium handling in patients with ESRD. In patients, however, the response to epinephrine was heterogeneous. In 4 of the 10 patients studied, epinephrine infusion did not result in a decrement in plasma potassium suggesting impaired beta-adrenergic responsiveness and thus blunting of this mechanism of extrarenal potassium disposal. In the remaining 6 patients, epinephrine infusion resulted in a fall in plasma potassium which was greater than that observed in normal subjects (1.13 +/- 0.14 and 0.63 +/- 0.07 mEq/l, respectively, p less than 0.01). In the presence of propranolol, the infusion of epinephrine did not result in a decrement in plasma potassium in these 6 patients or in the 6 normal subjects (0.04 +/- 0.07 and -0.02 +/- 0.06 mEq/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease: effect of propranolol. 287 4

Intravitreal injection of ouabain was used to induce unilateral hypotony and to study the relationship of adenylate cyclase (AC) and sodium-potassium activated adenosine triphosphatase (NaK-ATPase) both of which are involved in the production of aqueous humour. After preliminary experiments, days 3 and 5 were chosen as representative times when IOP was maximally reduced and stable following ouabain injection. NaK-ATPase and adenylate cyclase activities were measured biochemically in the same homogenates of isolated ciliary processes (CP). Biochemical measurements showed that 46% of NaK-ATPase activity was inhibited after 3 days, and about 78% of NaK-ATPase was inhibited 5 days after ouabain injection. At the beginning of NaK-ATPase inhibition there was a significant stimulation of adenylate cyclase activity of the CP. The highest activities were seen 2 and 3 days after ouabain injection. The suggestion is made that these 2 enzymes are interdependent.
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PMID:Stimulation of adenylate cyclase of ciliary processes in response to decreased inflow of aqueous humour. 299 86

Epinephrine was infused intravenously in 9 normal volunteers to plasma concentrations similar to those found after acute myocardial infarction. This study was undertaken on 3 occasions after 5 days of treatment with placebo or the beta-adrenoceptor antagonist, atenolol, which is relatively beta 1 selective, or timolol, which blocks both beta 1 and beta 2 receptors. Epinephrine increased the systolic blood pressure (BP), decreased the diastolic BP and increased the heart rate modestly. These changes were prevented by atenolol. However, after timolol the diastolic BP rose by +19 mm Hg and heart rate fell by -8 beats/min. Epinephrine caused the corrected QT interval to lengthen (0.36 +/- 0.02 to 0.41 +/- 0.06 second). No significant changes were found in the corrected QT interval when subjects were pretreated with atenolol or timolol. The serum potassium decreased from 4.06 to 3.22 mmol/liter after epinephrine. Serum potassium decreased to a lesser extent to 3.67 mmol/liter after atenolol and actually increased to 4.25 mmol/liter after timolol. In a further study with a similar design another nonselective beta blocker propranolol also increased potassium after epinephrine. While atenolol also prevented hypokalemia in this study, it did not block the beta 2-receptor mediated decrease in diastolic BP. Epinephrine-induced hypokalemia results from stimulation of a beta-adrenoceptor linked to membrane sodium/potassium adenosine triphosphatase causing potassium influx. This appears to be predominantly mediated by beta 2 receptors although beta 1 receptors may also play a part.
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PMID:Epinephrine-induced hypokalemia: the role of beta adrenoceptors. 301 Jun 93

Previous in vitro evidence suggests that adrenaline causes K influx in skeletal muscle by stimulating a ouabain sensitive Na/K ATPase membrane pump. However in rabbits, adrenaline induced hypokalaemia was not significantly altered by pretreatment with digoxin (50 micrograms/kg). Rats were infused with adrenaline or saline after being given a tracer dose of 42KCl. Adrenaline caused a highly significant uptake of 42K in skeletal muscle and a decrease in 42K uptake in ventricle. Rats were also studied after receiving a high dose of digoxin (1.4 mg/kg) which by itself produced a significant increase in plasma K, a decrease in plasma Na and a decreased uptake of 42K in ventricle and lung. These results suggest that adequate widespread Na/K ATPase inhibition had been achieved by this dose of digoxin but despite this, adrenaline still caused hypokalaemia and also still caused significant 42K tissue uptake by skeletal muscle. These results suggest that adrenaline causes K influx by skeletal muscle and K efflux by cardiac tissue. Furthermore, the former mechanism was not inhibited by pretreatment with digoxin.
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PMID:Adrenaline causes potassium influx in skeletal muscle and potassium efflux in cardiac muscle in rats: the role of Na/K ATPase. 302 40

The angles of ramp of normalized dependences: "strength-velocity" and "terminal systolic length--terminal systolic strength" proved to be lesser under physiological loads in isolated papillary muscles of newborn kitten as compared with adult cats. Adrenaline increased the slope of these dependences up to the values characteristics of the adult cat's myocardium in saline. The data obtained suggest a low level of the calcium activation and ATPase activity of contractile proteins of the myocardium in newborn kitten.
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PMID:[Myocardial contractility in newborn kittens under a physiologic loading regimen]. 321 31

1. We have previously shown that salbutamol induced hypokalaemia, like adrenaline induced hypokalaemia, is the result of stimulation of a membrane bound beta 2-adrenoreceptor linked to Na+/K+ ATPase. We have also demonstrated that adrenaline induced hypokalaemia is potentiated by therapeutic concentrations of theophylline. 2. In a single-blind study of 14 normal volunteers, we infused salbutamol in doses used in clinical practice and examined the effects of the addition of theophylline alone or combined with (-)-adrenaline on plasma potassium levels, heart rate and blood pressure. The combinations studied were (i) salbutamol + vehicle control adrenaline infusion + placebo theophylline; (ii) salbutamol + vehicle control adrenaline infusion + theophylline; (iii) salbutamol + adrenaline + theophylline. 3. In a randomised, balanced placebo controlled design oral slow release theophylline or placebo was given for 9 days. Subjects were studied twice on the active limb (days 7 and 9) and once on the placebo limb (day 9) and the procedure was identical on each of the 3 study days except for the solutions administered. 4. Theophylline increased salbutamol induced hypokalaemia and in some individuals profound hypokalaemia (less than 2.5 mmol l-1) was observed with these relatively low doses of salbutamol and theophylline. Adrenaline did not further increase the magnitude of the fall in potassium observed. Combining theophylline with salbutamol increased the tachycardia resulting from the salbutamol infusion. Salbutamol infusion caused a fall in diastolic and rise in systolic blood pressure on all 3 study days and this was not altered by either theophylline or adrenaline alone or together.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline. 340 37

Increased circulating adrenaline produces systemic hypokalaemia by the stimulation of a membrane bound Na/K ATPase. In man, this enzyme appears to be linked to an adrenoceptor of the beta-subtype. We have further studied the subtype of beta-adrenoceptor involved by infusing adrenaline intravenously in normal volunteers after pretreatment with either a selective beta 2 antagonist (ICI 118551) or placebo. During the adrenaline infusion the serum potassium fell from 4.08 +/- 0.21 to 3.32 +/- 0.25 mmol/l (P less than 0.002). This adrenaline induced hypokalaemia was completely blocked by ICI 118551 (3.82 +/- 0.13 to 4.03 +/- 0.22 mmol/l, NS). Adrenaline also caused electrocardiographic changes of T wave flattening (-1.8 +/- 1.5 mm, P less than 0.05) whereas the T wave height increased after ICI 118551 (+ 1.0 +/- 0.9 mm, P less than 0.05). This suggests that adrenaline acts via beta 2 adrenoceptors in man to cause potassium influx and systemic hypokalaemia.
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PMID:Adrenaline causes hypokalaemia in man by beta 2 adrenoceptor stimulation. 614 31


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