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)

Slices of submaxillary gland were incubated in vitro in an enriched Krebs-Ringer-bicarbonate medium gassed with 95% O2-5% CO2 at 37 degrees C and the release of K+ into the medium was monitored after stimulation with alpha and beta adrenergic secretagogues under a variety of experimental conditions. K+ was released by the slice system after addition of norepinephrine, epinephrine or phenylephrine, but not after addition of isoproterenol. The extent of K+ release after norepinephrine depends on the dose of secretagogue and is higher when glucose, adenine and inosine, or all three substrates are absent from the medium. The effect of norepinephrine on K+ release is reversed by phentolamine but not by propranolol. Phentolamine also causes a 9.4-fold shift to the right in the dose-response curve to norepinephrine. Addition of ouabain to the incubation medium results in a higher extent of K+ release and prevents the reversal caused by phentolamine. The response to norepinephrine fails to occur when Ca++ is absent from the medium, either by chelation with ethylene glycol bis (beta-amino-ethyl ether)-N,N'-tetraacetic acid or by elimination from the Krebs-Ringer solution, and shows gradations depending on the Ca++ content of the medium. By itself, however, Ca++ does not induce K+ release from the slice system. The following conclusions are derived from these observations: 1) the release of K+ ions from the submaxillary gland is mediated by alpha adrenergic receptors; 2) the net amount of K+ released is the result of two opposing and almost simultaneous mechanisms, a passive extrusion and an active reuptake; 3) the active reuptake of K+ depends on the availability of energy and is mediated through the ouabain-sensitive Na+-K+ activated adenosine triphosphatase; 4) the reaction is critically dependent on the presence of Ca++ in the incubation medium and probably involves an influx of Ca++ upon stimulation with alpha adrenergic secretagogues.
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PMID:Potassium release from the rat submaxillary gland in vitro. I. Induction by catecholamines. 0 65

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K(+)-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10(-6)-10(-4) mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10(-6), 10(-5) and 10(-4) mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10(-3) mol/l histamine (n = 6). In human bronchial rings, ouabain (10(-5) mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetraacetic acid) and nifedipine (10(-5) mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10(-5) mol/l) was without effect. 4. Ouabain (10(-5) mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10(-3) mol/l amiloride relaxing strips completely over 15 minutes (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of sodium-transport inhibitors on airway smooth muscle contractility in vitro. 217 51

A newly synthesized compound, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), was shown to be a potent inhibitor of two cyclic nucleotide-dependent protein kinases, cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein kinase and the Ki values were 1.4 and 2.3 microM, respectively. HA-1004 relaxed rabbit aortic strips contracted by various agonists and with similar ED50 values. Phenotolamine, propranolol and atropine did not affect this HA-1004-induced relaxation, thereby suggesting that this compound does not act through these membrane receptor associated mechanisms. HA-1004 shifted the dose-response curve for CaCl2 to the right in a competitive manner in depolarized rabbit renal arterial strips. This compound also relaxed the A-23187 and phenylephrine-induced contractions elicited in Ca++-free solution. These findings suggest that HA-1004 exerts its action at the intracellular or submembranal level. This vasodilator has little effect on actomyosin adenosine triphosphatase and Ca++-calmodulin-dependent myosin light chain kinase. Studies using its derivatives with various lengths of alkyl chain (C0-C6) indicated that the potencies of these compounds, as vasorelaxants, correlated well with their potential to inhibit cyclic nucleotide-dependent protein kinase. HA-1004 should be a useful tool for investigating in smooth muscle, regulatory mechanism(s) by second messengers, cyclic AMP and cyclic GMP.
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PMID:Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. 299 36