Na+-K+-adenosine triphosphatase

The catecholamines can play an important role in the short-term regulation of plasma potassium levels. Stimulation of hepatic a-adrenoceptors will result in the release of potassium from the liver. In contrast, stimulation of (32-adrenoceptors, particularly in skeletal muscle, will lead to the uptake of potassium into this tissue. The (32-adrenoceptors are linked to the enzyme Na"", K+ adenosine triphosphatase (ATPase). Excessive stimulation of these (32-adrenoceptors may produce hypokalemia, which in turn can be a cause of cardiac arrhythmias. 

Nurnberger J Jr, Jimerson DC, Allen JR, et al Red cell ouabain-sensitive Na -K -adenosine triphosphatase a state marker in affective disorder inversely related to plasma cortisol. Biol Psychiatry 17 981-992, 1982 Nutt D, Montgomery SA Moclobemide in the treatment of social phobia. Int Clin Psychopharmacol 11 (suppl 3 77-82, 1996 Nutt DJ, Glue P, Lawson GW, et al Elumazenil provocation of panic attacks evidence for altered benzodiazepine receptor sensitivity ion panic disorder. Arch Gen Psychiatry 47 917-925, 1990... 

Middleton JP, Raymond JR, Whorton AR, Dennis VW. Short-term regulation of Na+/K+ adenosine triphosphatase by recombinant human serotonin 5-HT1A receptor expressed in HeLa cells. J Clin Invest 1990 86 1799-1805. 

Inhibition of carbonic anhydrase also decreases sodium entry into the posterior chamber. Sodium, transported by Na+-K+-adenosine triphosphatase, probably acts as the counter-ion for newly formed bicarbonate. These two ions are linked such that inhibition of either carbonic anhydrase or Na+-K+-adenosine triphosphatase reduces sodium movement into the posterior chamber. 

Figure 10-14 Ion and fluid movement in the nonpigmented ciliary epithelium. Na+ enters the nonpigmented ciliary epithelium from the stromal side either by diffusion or by NaVH+ exchange. Na+, the main cation involved in aqueous formation, is transported extraceUularly into the lateral intercellular channel by a Na+-K+-adenosine triphosphatase-dependent transport system. HC03 forms from the hydration of CO2, a reaction catalyzed by carbonic anhydrase. HC03", the major anion involved in aqueous formation, balances a portion of the Na+ being transported into the lateral intercellular channel. Cl" enters the intercellular space by a mechanism that is not understood. This movement of ions into the lateral intercellular space creates a hypertonic fluid, and water enters by osmosis. Because of the restriction on the stromal side of the channel, the newly formed fluid moves toward the posterior chamber. A rapid diffusional exchange of CO2 allows for its movement into the posterior chamber. (Adapted from Cole DF. Secretion of aqueous humor. Exp Eye Res 1977 25(suppl) l6l-176.)...

The effect on lOP of the cardiac glycosides, primarily digitaUs derivatives and ouabain, has been of interest for many years. The physiologic effects of these agents are produced by their ability to inhibit Na+K+ adenosine triphosphatase, and a ouabain-sensitive Na+K+ adenosine triphosphatase has been demonstrated in the ciliary epitheUum. In the ciliary nonpigmented epithelium, as in other types of secretory epitheUum, Na+K+ adenosine triphosphatase is thought to be responsible for the active transport of sodium, a process necessary for aqueous secretion to occur. 

The nervous system is the main site of toxicity for DDT. Effects are observed on both the central nervous system (CNS) and peripherally. There is significant alteration of neuronal membrane enzymatic and electrophysiological properties. In particular, sodium channels are altered such that once activated they close slowly, prolonging the depolarization of the nerve by interfering with the active transport of Na ions out of the axon. Potassium channels are also affected. DDT specifically affects Na", K -adenosine triphosphatases (ATPases) and Ca " -AT-Pases, which inhibit repolarization of neurons. The membrane remains partially depolarized and is extremely sensitive to complete depolarization by very small stimuli. DDT also inhibits calmodulin that is necessary for Ca transport essential for the subsequent release of neurotransmitters. 

The Na -K ATPase Pump. The Na -K" " adenosine triphosphatase (ATPase) transport system is the primary active transport process that maintains the normal chemical gradients for Na" " and K" " in cells of both vertebrates and invertebrates. Although the concern of this article is with neuronal tissue, it should be stressed that the Na -K ATPase pump... 

Williams PD, Trimble ME, Crespo L, Holohan PD, Freedman JC, Ross CR. Inhibition of renal Na+, K -adenosine triphosphatase by gentamicin. J Pharmacol Exp Ther 1984 231 248-253. 

In the normal thyroid, NIS transports two Na and one V down the Na ion gradient generated by the activity of Na /K adenosine triphosphatase enzyme (ATPase) (Figure 102.2). If ATPase is blocked with ouabain, thyroid iodine uptake is also blocked. 

The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiological changes is still not completely known despite years of active investigation. Several mechanisms have been proposed, but the most widely accepted mechanism involves the ability of cardiac glycosides to inhibit the membrane-bound Na /K -adenosine triphosphatase (Na /K -ATPase) pump responsible for sodium/potassium exchange. To understand better the correlation between the pump and the mechanism of action of cardiac glycosides on the heart muscle contraction, one has to consider the sequence of events associated with cardiac action potential that ultimately leads to muscular contraction. The process of membrane depolarization/repolarization is controlled mainly by the movement of the three ions, Na", K", Ca ", in and out of the cell. 

Very few data are available with regard to metabolism of palytoxin in the animal/human body and its connection with toxicity. The main mode of palytoxin action (which is presented in detail in Chapter 34) is related to disruption of the mammahan cell sodium pump functionality. Targeting the Na, K -adenosine triphosphatase (ATPase) pump, palytoxin binds to the ATPase and converts the pump into a nonspecific ion channel, thereby, short-circuiting membrane function of the cell and eventually causing cell lysis [64]. 

Another possibility deserving consideration is that some of the phytoestrogen effects may be attributable to properties that do not involve estrogen receptors, such as effects on enzymes, protein synthesis, cell proliferation, angiogenesis, calcium transport, Na /K adenosine triphosphatase, growth factor action, vascular smooth muscle cells, lipid oxidation, and cell differentiation. Some of these properties will be further discussed. 

Postnov, Y.U., Reznikova, M. and Boriskina, G. (1976). Na-K-adenosine triphosphatase in the kidney of rats with renal hypertension and spontaneously hypertensive rats. Pflugers Arch., 362, 95-99... 

K. Atterwill, D. J, Atkinson, I. Bermudez, and R. Balazs, Effect of thyroid hormone and serum on the development of Na+,K+-adenosine triphosphatase and associated ion fluxes in cultures from rat brain. Neuroscience 14 361-373 (1985),... 

Both compounds were reversible inhibitors of (Na+ K ) adenosine-triphosphatase when assayed in dim light. The KiS were 1.3 itM for DAMN-cymarin and 0.9 joM for CM-cymarin. 

Fig. 2. Distribution of radioactivity covalently attached to (Na + K ) adenosine triphosphatase that has been photolyzed in the presence of [ ClCM-cymarin. Samples of enzyme that had been photolyzed either in the presence of the complete MgATP phosphorylating system (O) or the complete system plus a 25-fold excess of cymarin as protector ( ) were run on sodium dodecyl sulfate gels which were scanned, sliced, and counted. The A2M trace from the gel with the unprotected sample was divided into segments exactly as the gel had been sliced. The mean of each of these segments was calculated, and the values were plotted ( ). The units of are arbitrary since the scanner was uncalibrated. The three protein components are (a) cross-linked /3 dimer (b) large chain (c) small chain.

Raghavan, S.R.V., Culver, B.D., Gonick, H.C., 1981. Erythrocyte lead-binding protein after occupational exposure. II. Influence of lead inhibition of membrane Na, K -adenosine triphosphatase. J. Toxicol. EnviroiL Health 7, 561—567. 

Kaul S, Krishnakanth TP. Effect of retinol deficiency and curcumin or turmeric feeding on brain Na(+)-K+ adenosine triphosphatase activity. Mol Cell Biochem 1994 137 101-107. 

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