The effect of diphenylhydantoin administration on sodium‐potassiumivated ATPase in cortex

Lewin, Edward; Black, Virginia D.

doi:10.1212/wnl.21.6.647

Cited by 42 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fact that ouabain could reverse the DPH induced stimulation of K uptake at high Na and low K concentrations offers evidence that synaptosomal sodium-potassiumATPase may be involved. These results are in agreement with previous observations that synaptosomal and microsomal sodium-potassium-ATPase is stimulated by DPH under conditions of high sodium and low potassium concentrations (9)(10)(11).…”

Section: Resultssupporting

confidence: 93%

Diphenylhydantoin and potassium transport in isolated nerve terminals

Escueta¹,

Appel

1971

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The antiepileptic action of diphenylhydantoin (DPH) has been explained by two different theories: (a) that DPH stimulates the Na-K pump; (b) that DPH specifically blocks the passive translocation of sodium. Since electrophysiological experiments have recently suggested abnormal synaptic mechanisms as the basis for epileptogenic discharges, the action of DPH on K transport within synaptic terminals isolated from "normal" rat brain cortex was examined directly. A rapid filtration technique was used to assess in vitro potassium transport within synaptosomes. In vivo DPH did not significantly change endogenous K content within synaptosomes. With sodium (50 mM) and potassium (10 mM) concentrations optimal for Na-K pump activity, in vivo and in vitro DPH (10-' M) had minimal or no effects on total K uptake. DPH stimulated potassium uptake within synaptosomes under two situations: (a) at high sodium (50-100 mM) and low potassium (less than 2 mM) concentrations; (b) when synaptosomes were incubated with ouabain (10' M) 50 mm Na and 10 mm K. In both situations, K was leaking out of synaptic terminals and the enhancement in net K uptake roughly corresponded to the ouabain inhibitable segment. In the absence of ouabain, the stimulatory effects of DPH were not observed when K was 2 mM or higher and when Na was 10 mm or lower. The stimulatory effects of in vitro DPH appeared over a range of concentrations from 10-' to 10-M while single intraperitoneal injections of DPH had to be administered for 2 days before its effects were observed on synaptosomal K transport. The present data provided direct evidence for DPH stimulation of active potassium transport within synaptosomes under ionic conditions simulating the depolarized state. At other ionic conditions, DPH had inhibitory or no effects on K uptake. Although the results do not specify whether the effects Dr. Appel is the recipient of a Research Career Development Award from the U. S. Public Health Service.Received for publication 15 December 1970. of DPH on the Na-K pump are direct or indirect, they suggest that the action of DPH depends upon the state of the membrane and the specific ionic environment. INTRODUCTIONStudies of the mechanism of action of diphenylhydantoin sodium (DPH)1 have centered on the cation transport systems of excitable membranes of the cerebral cortex (1, 3). In whole cerebral cortical tissues, DPH prevented intracellular increase of Na caused by maximal electroshock seizures and increased the turnover of Nan' (1). Because of the close link established between membrane -oriented sodium -potassium -adenosinetriphosphatase (Na-K-ATPase) and cation transport (2), synaptosomal Na-K-ATPase was previously studied in an attempt to explain the Na extruding properties of DPH. DPH stimulated synaptosomal Na-K-ATPase activity under conditions of high Na (100 mM) and low K (0.2 mM) while it had minimal or no effects on enzyme activity with 50 mm Na and 10 mm K (3). On the basis of these experiments, it was suggested that the anticonvulsant prop...

show abstract

Section: Resultssupporting

confidence: 93%

Diphenylhydantoin and potassium transport in isolated nerve terminals

Escueta¹,

Appel

1971

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Recent conflicting findings of Danielson, Bittar, Chen & Tong (1971) who found that DPH inhibited Na efflux in barnacle muscles, and Lewin & Bleck (1971) who showed that DPH can stimulate kidney Na-K-ATPase, emphasize that no clear pattern regarding DPH has emerged. The increased intracellular 'Na with the addition of DPH shows that DPH increases the membrane permeability to Na.…”

Section: Discussionmentioning

confidence: 99%

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea‐pig heart

Baskin

Dutta

Marks

1973

British J Pharmacology

View full text Add to dashboard Cite

Summary1. Diphenylhydantoin (DPH) and potassium significantly prevent ouabain intoxication without preventing the inotropic effects of ouabain in the guineapig isolated heart. 2. The antiarrhythmic effect of DPH and K on ouabain-induced toxicity appears to be related to their ability to reduce ouabain accumulation by the myocardium and thereby prevent the intracellular Na and K changes which lead to the arrhythmic state.

show abstract

“…A report by Duncan et al (1968) demonstrated that prolonged intermittent electrical stimulation of the partially isolated cortical slab prevented the loss of acetylcholine esterase (ChE) (E.C.3.1.1.7) activity normally found in the undercut slab, and concurrently prevented the development of electrical hyperexcitability. A recent report by Lewin and Bleck (1971) described the effect of diphenylhydantoin on NaK-dependent ATPase (E.C.3.6.1.3.) alterations in cryogenic lesions.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Diphenylhydantoin on the Activity of Selected Enzymes in Chronic Isolated Cerebral Cortex of Cat

et al. 1973

View full text Add to dashboard Cite

SUMMARY The effect of diphenylhydantoin, an anticonvulsant, on the specific activity alterations of enzymes related to function, membrane stability and energy processes in the chronic isolated cerebral cortex of the cat as a function of time after undercutting is described. Data are also presented demonstrating the action of diphenylhydantoin on the development of hyperexcitability in terms of duration of afterdischarge monitored by surface‐recording post stimulus. RÉSUMÉ Ľactivité enzymatique était mesurée sur le cortex isolé de chats jusqu'au vingthuitième jour et chez des chats de contrôle. La diphénylhydantoïne diminuait le taux de monoamine oxidase qui résultait de la section sous piale mais elle n'affectait pas ľactivité des autres enzymes (déhydrogénase succinique, Na/K‐dependant ATPase, choline acétylase et acétylcholine esterase). Dans le cortex normal et dans le cortex isolé hyperexcitable, la diphénylhydantoïne diminuait la durée de la post‐décharge. ZUSAMMENFASSUNG Die Enzymaktivität wurde im unterschnittenen Cortex von Katzen bis zu 28 Tagen nach dem Eingriff und bei Kontrollen gemessen. Diphenylhydantoin vermindert den Anstieg der Monoaminooxidase als Folge der Unterschneidung. Es hat jedoch keine Wirkung auf die Veränderung der Aktivität anderer Enzyme (Succinyldehydro‐genase, Natrium‐Kalium abhängige ATPase, Cholinacetylase und Acetylcholinesterase). Sowohl im normalen wie im hyperexcitablen unterschnittenen Cortex vermindert Diphenylhydantoin die Dauer der Nachentladung. RESUMEN Se mide la activadad encimática en el cortex crónicamente aislado del gato a lo largo de 28 diás. La difenilhidantoína disminuye el aumento de la monoaminoxidasa que se produce al aislar el cortex, pero no modifica los cambios de actividad de otras encimas (dehidrogenasa succínica, Na/K‐ATPasa, acetilasa colínica y esterasa acetilcolínica). Tanto en el cortex normal como en el aislado hiperexcitable, la difenilhidantoina disminuye la duratión de las post‐descargas.

show abstract

The effect of diphenylhydantoin administration on sodium‐potassiumivated ATPase in cortex

Cited by 42 publications

References 0 publications

Diphenylhydantoin and potassium transport in isolated nerve terminals

Diphenylhydantoin and potassium transport in isolated nerve terminals

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea‐pig heart

The Effect of Diphenylhydantoin on the Activity of Selected Enzymes in Chronic Isolated Cerebral Cortex of Cat

Contact Info

Product

Resources

About