Inhibition of Na+,K+-ATPase

Peng, M., Huang, L., Xie, Z., Huang, W. H. and Askari, A. Partial inhibition of Na+/K+-ATPase by ouabain induces the Ca2+-dependent expressions of early-response genes in cardiac myocytes. /. Biol. Chem. 271 10372-10378,1996. 

Some of these environmental aspects are obvious, such as anthropogenic sources of chemicals that disrupt the structure of delicate epithelia involved in solute transport, or directly inhibit the solute transporting proteins (e.g. Cu inhibition of Na+K+ ATPase [82]). The general effects of environmental stress are also well known, since many of the hormones released into the blood during stressful situations will alter the activity of ion transporters (e.g. corticosteroids, catecholamine [14]). 

Mercuric chloride gives a decrease in monoamine [85, 92] and choline [92] uptake in brain synaptosomes which may be related to an inhibition of Na+/K +-ATPase [85, 92-94]. 

Mercuric chloride may induce catecholamine release from adrenals. The initial phase may be due to amine displacement by the mercury ion but the secondary phase probably involves alteration of membrane structures [95]. Mercury compounds have also been shown to increase the efflux of monoamines from mouse striated slices [96] and from adrenergic nerve fibre terminals [97], the effect being attributed to inhibition of Na /K+-ATPase activity and(or) disruption of intracellular Ca2+ regulatory mechanisms [96]. 

The mechanism of action of these drugs is not completely understood. However, it is very likely that they inhibit cellular phosphodiesterase of the myocardium, which leads to an elevation in the cellular level of cyclic AMP, which in turn facihtates contraction of myocardial cells. It is clear that these drags are not 8-adrenoreceptor antagonists, and that their effect is not mediated by inhibition of (Na -K+) ATPase. They simultaneously increase the flow of calcium ions into the cell. They are used for short-term control of patients that inadequately react to cardiac glycosides, diuretics, and coronary vasodilating agents. 

Nobel CS, Aronson JK, van den Dobbelsteen DJ, Slater AF. Inhibition of Na+/K(+)-ATPase may be one mechanism contributing to potassium efflux and cell shrinkage in CD95-induced apoptosis. Apoptosis 2000 5(2) 153-63. 

Cardiac glycosides affect all excitable tissues, including smooth muscle and the central nervous system. Inhibition of Na+/K+ ATPase in these tissues depolarizes and increases spontaneous activity both in neurons and in smooth muscle cells. The gastrointestinal tract is the most common site of digitalis toxicity outside the heart. The effects include anorexia, nausea, vomiting, and diarrhea. 

Kramer HJ, Gonick HC, Lu E. 1986. In vitro inhibition of Na-K-ATPase by trace metals Relation to renal and cardiovascular damage. Nephron 44 329- 336. 

Drag-Membrane Interactions and Inhibition of Na+,K+-ATPase 220 5.1.2 Release of Pharmacological Response 223... 

The inhibition of Na+, K+-ATPase by VC>4 has been developed as an assay for vanadium in serum samples84,85 . 

Harmaline Inhibition of Na. K -ATPase, Na transport, and monoamine oxidase A 375,376... 

These results provide additional evidence that enzyme repression is an important mechanism in B(a)P-induced neurotoxicity and likely results from oxidative stress in the nervous system. Inhibition of Na /K -ATPase, an important enzyme in muscle contraction and nerve excitability, in addition to decreased motor conduction velocities may explain the suppression of motor activity observed in B(a)P intoxicated rats (Kim et al, 2000 Saunders et al, 2001). Furthermore, there is also strong experimental evidence showing that oxidative stress and lipid peroxidative products can cause decreases in dopamine and inhibit Na /K -ATPase activity as well (Madrigal et al, 2003). 

Digoxin, the most commonly used cardiac glycoside, is indicated for the treatment of CHF and for the treatment of supraventricular tachyarrhythmias. It possesses positive inotropic and electro-physiological effects resulting from the inhibition of Na, K -ATPase, which increases intracellular sodium ion concentrations. This increase in intracellular sodium ions slows down calcium extrusion from the cell, resulting in an increase in intracyto-plasmic calcium and, thereby, an increase in the contractile force. 

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