Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart.

Under certain conditions, taurine (3.0mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K+ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca++ content in the heart. Taurine in the heart was not directly related to this potentiation.     

Inhibitory effect of taurine on decrease in the inotropic action of ouabain at high concentrations in isolated atria

Summary In vitro, taurine was shown to inhibit the decrease in the inotropic effect of ouabain at large doses in the normal and also low K⁺ medium in which this decrease in the inotropism of ouabain was facilitated. This inhibitory effect of taurine was, at least in part, due to the inhibition of the efflux of intracellular K⁺ in the isolated heart.     

Tetanus toxin does not affect the release of noradrenaline and taurine from rat cerebral cortex slices evoked by high K+ and Na+-free media

Noradrenaline and taurine release from superfused rat cerebral cortex slices was stimulated by potassium ions, veratrine, ouabain and omission of sodium ions. Tetanus toxin enhanced only the ouabain-evoked calcium-dependent noradrenaline release and the ouabain-evoked calcium-independent taurine release. The uptake of both was marginally affected.     

Effect of taurine on mitogen response of human lymphocytes

Summary Taurine selectively inhibits the phytohemagglutinin-stimulated incorporation of³H-thymidine by human cultured lymphocytes (50% inhibition by 12.5 mM taurine). Decreasing effects of taurine on Na–K ATPase activity or on calcium accumulation by lymphocytes might be responsible for its action on cell proliferation.Thanks are due to Mr F. Cervantes Salas for technical assistance. This work was partly supported by grants. No. 5 RO1-EY 02540-02 from the National Eye Institute and No. PCCBNAL 790219 from CONACyT.     

Tetanus toxin does not affect the release of noradrenaline and taurine from rat cerebral cortex slices evoked by high K+ and Na+-free media

Summary Noradrenaline and taurine release from superfused rat cerebral cortex slices was stimulated by potassium ions, veratrine, ouabain and omission of sodium ions. Tetanus toxin enhanced only the ouabain-evoked calcium-dependent noradrenaline release and the ouabain-evoked calcium-independent taurine release. The uptake of both was marginally affected.     

The activation of membrane ATPase by ouabain in several tissues of the golden hamster (Mesocricetus auratus) in the absence of potassium

Summary The activity of the membrane ATPase of 5 organs of the golden hamster was increased by 10^–7–10^–3 moles/l ouabain in K⁺-free medium. In similar experiments on rats no increase was observed.     

Effect of in vivo irradiation of the rat on the taurine concentration of the heart

Summary The taurine concentration in the heart of the rat (moles/g of tissue) was not modified during 10 days after an in vivo irradiation of 900 R.     

Some factors affecting Malpighian tubule fluid secretion and transepithelial potential inLocusta migratoria L.

Summary Both fluid secretion and transepithelial potential were stimulated by cAMP. Fluid secretion was unaffected by 5-HT over the concentration range 10^–8–10^–4 M. The presence of ouabain in the bathing medium effected a decrease in transepithelial potential.     

Digoxin and ouabain increase the synthesis of cholesterol in human liver cells

Digoxin and ouabain are steroid drugs that inhibit the Na⁺/K⁺-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver HepG2 cells, enhancing the activity and the expression of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver cells. Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009     

Influence of bistramide A on the twitch tension in rat atrial heart muscle

Bistramide A, a new toxin isolated from the UrochordateLissoclinum bistratum Sluiter, was applied to rat auricular heart muscle bundles. At a stimulation frequency of 0.2 Hz, the toxin induces a dose-dependent reduction of the stimulated twitch tension force; it decreases and shortens the duration of the plateau and the slow repolarizing phase of the action potential. In the control solution, switching from a stimulation frequency of 0.2 Hz to 1 Hz decreases the force with which a positive potentiation develops either at a maintained high frequency or after switching from 1 Hz to 0.2 Hz. Bistramide A reduces both the force evoked at 1 Hz and the potentiation. The data suggest that Bistramide A blocks Na⁺ conductance; inhibits Ca⁺⁺ channels in a time-and frequency-dependent manner; reduces Na⁺–Ca⁺⁺ exchange activity; but does not modify the ability of the sarcoplasmic reticulum to be refilled although the rate of Ca⁺⁺ accumulation is decreased.     

Ouabain-induced release of extraneuronal catecholamine in the isolated guinea-pig vas deferens

Summary It was found that ouabain (10^–5 M) was effective in releasing the extraneuronal catecholamine which was taken up by uptake₂ process in the guinea-pig vas deferens. This result shows that a Na–K ATPase is essential for the storage of catecholamine in the extraneuronal site.     

Action of juvenile hormone on the follicle cells ofRhodnius prolixus: Evidence for a novel regulatory mechanism involving protein kinase C

Summary Juvenile hormone (JH) is known to act on the membranes of the follicle cells ofRhodnius, activating a specific Na⁺, K⁺-ATPase. This leads to a decrease in volume of the cells and the appearance of spaces between them (patency). The addition of an inhibitor of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), to the medium in vitro inhibits the action of JH on the follicle cells. PDBU (phorbol-12,13-dibutyrate) mimics the action of JH in vitro and the response of the follicle cells to, PDBU is blocked by ouabain. It is concluded that the activation of protein kinase C is a required step in the chain of events leading to activation of the JH-dependent ATPase and set in train by the binding of JH to the membrane.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

Summary The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to ist specific antagonizing action on the Na⁺-K⁺-ATPase in the gastric mucosa.     

Endogenous oscillatory activity and TTX-sensitive spikes of the heart muscle in early juveniles of the isopod crustaceanLigia exotica

The heart beat of early juveniles of the littoral isopodLigia exotica occurred at a frequency of 250 to 350/min, associated with rhythmic activity of the heart muscle. Each burst was composed of a slow depolarizing potential with superimposed spike potentials. The spike potential was eliminated by perfusion with TTX-containing or Na⁺-free saline. In TTX-saline, the slow potential was unchanged in frequency and amplitude. By current injection into the heart muscle, the rhythm of the slow potential was phase-shifted and its frequency was changed in a membrane potential-dependent manner. These results show that the heart ofLigia early juveniles acts as an endogenous muscle oscillator generating oscillatory slow potentials and Na⁺-dependent spikes.     

Decrease in [3H]ouabain binding sites in heart and brain from spontaneously hypertensive rats

Summary A decrease in the number of binding sites (B_max) for [³H]ouabain was observed in the heart (37%) and the brain (22%) of spontaneously hypertensive rats (SHR) when compared with age-matched control Wistar Kyoto rats. No variation was detected in the affinity constant (K_D).     

Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates

Summary Chicken spinal cord adenosine triphosphatases (both Na⁺, K⁺ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.     

Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip

Summary Crude kallikrein (Padutin^®), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.The authors are greatful to Prof. G. L. Haberland, Bayer AG, Elberfeld (BRD), for his generous gift of pure Kallikrein^® KZC 1/75; to Bayer, Leverkusen (BRD), for Padutin^® and to Squibb, New Jersey, USA, for SQ 20881. This work is supported in part by Eczacibai Research Foundation, Levent, Istanbul, Turkey. The technical assistance of Mr. M. Kabaçam is greatly appreciated.     

Ouabain action on sodium,chloride and fluid transport in rabbit jejunum and ileum

Riassunto É stato studiato l'effetto della ouabaina sul trasporto di Na, Cl e fluido in digiuno e ileo isolato di coniglio. Mentre in entrambi i tratti intestinali il flusso mucosa-serosa di Na è inibito dal glicoside, il flusso nello stesso senso di Cl, di cui è stata dimostrata una componente attiva, non viene modificato. Poichè inoltre il trasporto di fluido viene inibito dalla ouabaina in misura diversa in digiuno e in ileo, si suggerisce la presenza di sistemi ATPasici non ouabaino-sensibili accanto alla Na–K ATPasi sensibile alla ouabaina che si ammette essere responsabile del trasporto di Na.

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Experiments not reported in this paper show that ouabain 5×10^–4 M does not enhance the ileal Na influx inhibition and also does not modify the Cl influx. Moreover ouabain 10^–4 M affects jejunal Na influx to a less significant extent than 5×10^–4 M.     

Effetto della ouabaina sul tessuto nervoso in coltura in vitro

Summary The addition of 1 · 10^–4 ouabain (strophantin-G), a Na⁺-K⁺-dependent ATP-ase inhibitor, to the cultivating medium of chick embryo spinal ganglia in vitro cultures caused the vacuolization of the cytoplasm of the fibroblast-like cells, but not of the nervous ones, after 6 h of culture, with a maximum after 24 h.     

Differences in membrane ion transport between hepatocytes from the periportal and the pericentral areas of the liver lobule

We studied the Na⁺/K⁺ pump, Na⁺/K⁺ ATPase activity, and oxygen consumption (QO₂) in hepatocytes isolated from the periportal (PH) and pericentral (CH) regions of the liver lobule, to provide an insight into the functional properties of these cells. Na⁺/K⁺ pump activity was determined using⁸⁶Rb⁺ (a functional analog of K⁺) and ouabain, a specific inhibitor of this transport system. Our results indicate the the Na⁺/K⁺, pump and Na⁺/K⁺ ATPase activity are significantly lower in CH than in PH, although basal ouabain-sensitive (OS) QO₂ was negligible in both of these cell preparations. However, OSQO₂ was significantly lower in CH than in PH when the Na⁺/K⁺ pump was activated using the ionophore nystatin in a Na⁺-containing medium. These results indicate that the differences in membrane ion transport exist between hepatocytes from different locations of the liver lobule.