Sodium uptak

Yeo, A.R., Yeo, M.E. Flowers, T.J. (1987). The contribution of an apoplastic pathway to sodium uptake by rice roots in saline conditions. Journal of Experimental Botany, 38, 1141-53. 

Initial inhibition of sodium uptake and whole body sodium content that were normal by day 28. Abnormal liver enzyme activity. Liver copper increased from 23 mg/kg FW at start to 113 mg/kg FW at day 28... 

Spiro compounds 202 and 203 are antagonists of the mineralocorticoid receptor. This limits the production of excess aldosterone, which, in turn, leads to increased sodium uptake and potassium loss. This condition, known as Conn s syndrome, is associated with hypertension <2005W02005110992>. Amine 204 is a seratonergic 5-HY5-HT2 agonist for the treatment of glaucoma <2003W003051352>. 

Further studies have revealed that pumiliotoxin B interacts with voltage-dependent sodium channels to elicit an increased influx of sodium ions (101,102) and, in brain and heart preparations, a stimulation of phosphoino-sitide breakdown (101,103-106). The phosphoinositide breakdown can, via inositol trisphosphate, cause release of calcium from internal storage sites. The cardiotonic activity of pumiliotoxin B and various congeners and synthetic analogs correlates well with the stimulation of phosphoinositide breakdown (104,105). A number of studies on stimulation of sodium uptake by pumiliotoxin B and inhibition by local anesthetics and other agents have appeared (106-108). The effects of pumiliotoxin B on neuromuscular preparations have been reinterpreted as due primarily to effects on sodium channels, although additional direct effects on calcium mobilization remain possible (109). It has recently been proposed that pumiliotoxin B enhances the rate of activation of sodium channels (110). One characteristic effect of pumiliotoxin B is to elicit repetitive firing in neurons, apparently because of effects on sodium channel function (109-111). 

Pyrethroid insecticides (deltamethrin, NRDC 157, cismethrin), DDT analogs ( p,j> -DDT, (>,j> -DDT, methoxychlor, EDO), and a DDT-pyrethroid hybrid compound (GH401) enhanced veratridine-dependent sodium uptake by mouse brain synaptosomes The effectiveness of these compounds in the sodium uptake assay was in good agreement with their acute mammalian toxicities. , -DDT also enhanced veratridine-dependent sodium uptake by fish brain synaptosomes These findings demonstrate the utility of ion flux assays to study interactions of insecticides with sodium channels in the central nervous system and to explore species differences in insecticide target site sensitivity ... 

In this paper, we report that DDT and its analogs, as well as pyrethroids, enhance veratridine-dependent sodium uptake in mouse brain synaptosomes. We also demonstrate the extension of these methods to study insecticide effects on sodium channel function in rainbow trout. 

Sodium uptake assay. Assays using mouse brain synaptosomes were performed as described previously (6., ), except that insecticides were introduced to resuspended synaptosomes in 0.2-0.4 yl of ethanol rather than as a residue in the incubation tube. This amount of ethanol improved the delivery of insecticides, thereby increasing the reproducibility of the assay, and had no measurable effect on veratridine-dependent sodium channel activation. These methods were also used for assays with fish brain membranes, except that all buffers were augmented with sucrose to give osmolarities equivalent to the 0 7 M sucrose used for membrane isolation. 

Table I. Effect of Deltamethrin on Basal and Veratridine-Stimulated Sodium Uptake by Mouse Brain Synaptosomes...

Figure 1. Effects of veratridine (VTD) concentration on veratridine-stimulated sodium uptake by mouse brain synaptosomes in the presence and absence of deltamethrin (DTM 10 yM) ...

Data points are means of two replicate experiments using different membrane preparations corrected for veratridine-independent sodium uptake Tabulated values are KQ concentration giving half-maximal uptake in yM E, maximum uptake at saturating concentrations in nmol/mg protei8 x Data are from ref. 10. 

Concentration giving half-maximal enhancement of veratridine-stimulated sodium uptake. 

Figure 2. Enhancement of veratridine-stimulated sodium uptake in mouse brain synaptosomes by pyrethroids and DDT analogs Each value is the mean of three determinations using different membrane preparations corrected for veratridine-stimulated uptake in the absence of insecticide bars show standard errors. Compound abbreviations DTM (deltamethrin) CM (cismethrin) MC (methoxychlor). Concentrations were 100 PM for all compounds except DTM (10 pM).

DDT significantly enhanced veratridine-dependent uptake at all veratridine concentrations above 10 pM, and maximum sodium uptake in the presence of both compounds was achieved at 50 pM, which is the approximate for veratridine alone These findings suggest that , -DDT notuonly enhances veratridine-dependent activation but also increases the potency of veratridine. This result contrasts with the interaction of deltamethrin and veratridine in mouse brain synaptosomes (Figure 1) where the insecticide enhanced activation but did not affect the potency of the activator The only previous report of insecticide-dependent potency shifts in sodium channel activation is in neuroblastoma cells, where pyrethroids increase the potency of batrachotoxin and dihydrograyanotoxin II as sodium channel activators, but do not alter the potency of veratridine (5). These experiments provide the basis for further studies to compare directly the selectivity and sensitivity of sodium channels from mammalian and fish brain in their interactions with insecticides ... 

Figure 4. Sodium uptake by fish brain synaptosomes BKG, background uptake VTD, uptake stimulated by 50 pH veratridine VTD+DDT, enhancement of veratridine-stimulated uptake by 100 pM DDT VTD+TTX, inhibition of veratridine-stimulated uptake by 5 pM tetrodotoxin. Values are means of three determinations using different membrane preparations bars show standard errors.

Our preliminary results with fish brain preparations suggest that ion flux techniques may be valuable in studies of target site differences between species. We have demonstrated veratridine-stimulated, tetrodotoxin-sensitive sodium uptake in a vesicular preparation from fish brain, thus confirming the presence of functional sodium channels in this preparation. Our results with , -DDT in this system also agree well with the action of DDT analogs and pyrethroids in mouse brain assays. Further studies wih both preparations should allow the exploration of target site differences between mammals and fish that have been inferred from whole animal toxicity studies. 

There appears to be no control of the absorption of dietary sodium, which essentially is totally absorbed, provided that glucose is available for transport processes. Sodium absorption takes place by several mechanisms, of which electroneutral cotransport subsystems account for about 20%, diffusion possibly for up to 50%, and other transport processes for the remainder. Sodium-glucose and sodium-amino acid cotransporters exist in the apical membranes of erythrocytes and mediate sodium uptake coupled to glucose or amino acid uptake. Thus, the absorption of glucose and some amino acids is dependent on sodium uptake. 

Sodium is thus central to the management of two of the most widespread clinical problems hypertension (in humans) and diarrhea. Indeed, the World Health Organization (WHO) regards the discovery of oral rehydration, which depends on restoration of enteric sodium uptake, as the main life-saving development in twentieth century medicine. This powerful clinical application rests on a simple physiological observation concerning an elementary but vital dietary constituent. 

Lockau W and Pfeffer S (1982) A cyanobacterial ATPase distinct from the coupling factor of photophosphorylation. Z. Naturforsch. 37c, 658-664. Paschinger H (1977) DCCD-induced sodium uptake by Anacystis nidulans. Arch. Microbiol. 113, 285-291. 

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