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Query: UMLS:C0027960 (mole)
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Naked mole rats, Heterocephalus glaber, have no obvious source of cholecalciferol (D3) available to them, given their underground habitat and tubiferous diet. They have undetectable levels of 25-OH-D3 and as such appear to be naturally deplete in D3. The effect of an oral D3 supplement on mineral balance and homeostasis was therefore investigated. This D3 treatment did not affect circulating levels of Ca2+ and inorganic phosphorus (P(i]. Nor did D3 treatment affect mineral intake and absorption. The Ca2+ and P(i) present in the food was efficiently extracted and absorbed, resulting in an apparent fractional absorption (AFA) efficiency exceeding 98%. Irrespective of D3 treatment, the amount of Ca2+ and P(i) absorbed was positively correlated with the amount ingested, suggesting that intestinal uptake is by a passive D3-independent process. After D3 supplementation urinary Ca2+ secretion was unchanged; however, the amount of P(i) excreted in the urine increased (P less than or equal to 0.05). This resulted in a concomitant decline in P(i) AFR (P less than or equal to 0.02 from 99.95 +/- 0.02% to 99.82 +/- 0.03%). Almost all the Ca2+ and P(i) in the glomerular filtrate were reabsorbed, facilitating AFR efficiencies that approach physiological maxima (greater than 99%). Changes in AFR efficiency with D3 supplementation are therefore of no biological significance. Net mineral flux of both elements, irrespective of D3 treatment, was positive. It is speculated that the ever-growing incisors of these animals act as mineral dumps and assist in the tight regulation of plasma Ca2+ and P(i). These data suggest that naked mole rats utilize mechanisms independent of D3 in regulating mineral homeostasis and are therefore well-adapted to an environment devoid of sunlight.
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PMID:Cholecalciferol has no effect on calcium and inorganic phosphorus balance in a naturally cholecalciferol-deplete subterranean mammal, the naked mole rat (Heterocephalus glaber). 185 11

1. The efflux of labelled sodium as well as net sodium and lithium changes were studied in aged high sodium sartorius muscles of the South American frog Leptodactilus ocelatus.2. In the presence of 2.5 mM potassium in the media, the replacement of external sodium with lithium or magnesium resulted in an increase in sodium efflux. The magnitude of such increase was always larger in lithium.3. With the absence of potassium in the media, the response of sodium efflux to replacement of external sodium varied with the cation used as a substitute. In lithium Ringer there was always a noticeable increase, whereas in magnesium there was always a marked reduction. The same results were observed when calcium was substituted for magnesium.4. The replacement of 60 mM external sodium with sucrose did not prevent the stimulating effect of 5 mM potassium on sodium efflux, nor the inhibitory action of 10(-4)M ouabain. This indicates that neither sucrose by itself, nor the lowering of the ionic strength, modified to an appreciable extent the function of the sodium pump.5. Net sodium extrusion took place against an electrochemical gradient in potassium-free - 50 mM sodium - mM lithium Ringer. About 75% of this efflux was ouabain sensitive.6. Muscles made both sodium and lithium rich and incubated in potassium-free - 60 mM sodium - 50 mM lithium Ringer also showed net sodium extrusion against an electrochemical gradient, which was 85% ouabain sensitive. This extrusion took place even under conditions where the changes in free energy favouring lithium entry were always lower than the changes in free energy opposing sodium going out. This indicates that a sodium-lithium exchange by a counter-transport process is unlikely.7. External potassium reduced the ouabain sensitive lithium influx in muscles incubated in lithium Ringer. The values found were 5.90 +/- 0.39 mu-mole/g.hr and 2.66 +/- 0.43 mumole/g.hr in potassium-free and 15 mM potassium respectively. At the same time potassium had no effect on the ouabain-insensitive lithium uptake.8. Muscles incubated in potassium-free-magnesium Ringer had a residual sodium efflux which could not be accounted for by passive movement. About 40% of it was abolished by 10(-4)M ouabain. This ouabain-sensitive part could be a consequence of some stimulation of the sodium pump by potassium leaking out of the cells. If this is correct it should be inhibited by external sodium and should not contribute to the total sodium efflux in potassium-free sodium media.9. Magnesium was used as the reference cation to study the sodium-stimulated sodium efflux under potassium-free conditions. The total sodium efflux amounted to 0.668 hr(-1) (rate constant) and was 71% ouabain sensitive.10. The present experiments demonstrated that lithium ions have a direct stimulating effect on sodium efflux in high sodium skeletal muscle, and strongly support the notion that this effect is produced by an activation of the sodium pump through a potassium-like action.
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PMID:Further evidence for a potassium-like action of lithium ions on sodium efflux in frog skeletal muscle. 463 26

1. The patterns of the free plasma amino acids in the pregnant guinea-pig and her foetuses, near term, are described. The concentration of each amino acid was higher in the foetal plasma than in the maternal. The foetal:maternal gradients (F:M) varied for each amino acid; the straight chain amino acids had the highest F:M ratios.2. Net transfer of endogenous plasma amino acids, from the maternal circulation across the placental membrane, was studied. The foetus was removed and the foetal placenta perfused in situ via the umbilical arteries, with an artificial fluid containing varying concentrations of amino acids.3. All the amino acids, both essential and non-essential, could be transferred from the maternal to the foetal circulation against the F:M gradients. With ;closed circuit' perfusion, this transport increased the concentration of total amino N in the perfusate until it was twice that of the normal F:M gradient of 5. The concentrations of the individual amino acids was increased to 1.7-4.2 times those normally present in foetal plasma, and the final values reached were similar to the concentrations of free amino acid found in placental tissue.4. The umbilical vein-artery differences were small, with the placenta perfused ;open circuit' in the steady state, using physiological flow rates and amino acid concentrations. The average net placental transfer of amino N found was 1.14 m-mole min(-1). This is about 60% of the calculated net rate of accumulation of N by the 60 g guinea-pig foetus.5. The influence of foetal placental perfusion concentration on transfer was small but significant. In the steady state, the transfer of amino N, and each individual amino acid, was found to be inversely proportional to the concentrations in the perfusate when the placenta was perfused ;open circuit'. The slopes of the regression of transfer on concentration had an average value of 0.13 n-mole min(-1) g(-1) per mumole. No significant difference in the slopes was found between the three amino acid transport groups.6. Net transfer was independent of perfusate flow, within the physiological range, which suggests a secretory process across the membrane from maternal to foetal circulation.
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PMID:Net placental transfer of free amino acids against varying concentrations. 476 95

1. Spleen slices pre-incubated for different periods at 4 degrees C in Krebs solution containing varying concentrations of calcium, up to 96 mM, lost their endogenous noradrenaline stores when reincubated in normal Krebs solution at 37 degrees C for 2 hr. Rate of loss of noradrenaline was roughly related to the calcium concentration of the pre-incubation medium and the pre-exposure time.2. Pre-treatment with isotonic barium or strontium (96 mM) Krebs solution also induced release of noradrenaline from spleen slices when re-exposed to normal Krebs solution. Barium was more effective than either calcium or strontium.3. The enhanced release induced by calcium pre-treatment occurred in the absence of calcium, with or without EGTA.4. Tissue calcium concentration of spleen slices was 0.68 m-mole/kg. Pre-treatment of slices with normal or 96 mM calcium-Krebs solution for 4 hr at 4 degrees C increased the calcium concentration to 2.57 and 9.9 m-mole/kg, respectively.5. Ouabain, which caused a dose-dependent release of noradrenaline, did not modify the release induced by calcium pre-treatment.6. Spleen slices prepared from cats anaesthetized with sodium pentobarbitone instead of ether were resistant to noradrenaline depletion by calcium pre-treatment.7. Evoked release of [(3)H]noradrenaline by high potassium from calcium-pre-treated slices did not occur in the absence of external calcium, even though the calcium pre-treatment enhanced the tissue concentration of this ion by nearly tenfold.8. Net uptake of noradrenaline in normal and in treated slices whose noradrenaline content was severely reduced by barium pre-treatment or sodium withdrawal was comparable.9. Specific activity of released and endogenous [(3)H]noradrenaline increased as the tissue stores of noradrenaline were reduced.10. It is suggested that the spontaneous loss of tissue noradrenaline after pre-treatment with high-calcium solution was due to inhibition of sodium-potassium-activated ATPase by intracellular accumulation of calcium ions. Evidence is presented to suggest that vesicles depleted of their endogenous transmitter by pre-treatment with calcium, strontium or barium, or by sodium withdrawal, are re-used for the storage and release of exogenous noradrenaline.
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PMID:Release of noradrenaline from slices of cat spleen by pre-treatment with calcium, strontium and barium. 477 3

The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/ml. In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P=<0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production. It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.
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PMID:Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. 480 35

1. Segments of rat diaphragms were kept in choline-free media for 4 hr and were then exposed to a physiological concentration of [(14)C]-choline (30 muM) at 37 degrees C. The synthesis, storage and subsequent release of [(14)C]acetylcholine by the muscles was assessed by isotopic- and bio-assays after isolation of the transmitter by paper electrophoresis.2. Replacement of endogenous acetylcholine (0.92 mu-mole/kg) with labelled acetylcholine proceeded slowly at rest, but rapidly during nerve stimulation. [(14)C]Acetylcholine accumulated most rapidly when hydrolysis of the released transmitter, and thus the re-use of endogenous choline, was prevented by an esterase inhibitor. Fully replaced stores were maintained during nerve stimulation by synthesis rates sufficient to replenish at least 35% of the store size in 5 min.3 In the presence of hemicholinium-3, which inhibits choline uptake, acetylcholine stores declined rapidly during stimulation, and residual synthesis was slight, indicating little intraneural choline. Net choline uptake into nerve terminals was estimated from the highest observed synthesis rate and from previous measurements of the number and size of terminals, as 3-6 p-mole/cm(2) sec.4. Transmitter synthesis was localized in the region of end-plates, and was reduced to a few per cent of normal 6 weeks after phrenic nerve section. Release experiments suggested that at least half of the acetylcholine in phrenic nerves is in their terminals; from this content and the morphology of the terminals, the average concentration of transmitter in the whole endings would appear to be about 50 m-mole/l. Homogenization of the muscles freed choline acetyltransferase into solution, but left some [(14)C]acetylcholine associated with small particles, presumably synaptic vesicles.5. Resting transmitter release was about 0.013% of stores/sec. With 360 nerve impulses at 1-20/sec, release increased up to 0.43% of stores/sec, and amounted to 3.5-7 x 10(-18) moles per end-plate per impulse. The release rate was unaffected by the doubling of store size which occurred with eserine, but the extra transmitter did help to maintain releasable stores during prolonged stimulation. Experiments with fractional store labelling indicated that newly synthesized acetylcholine was preferentially released.6. Preformed [(3)H]acetylcholine was not taken up and retained by muscle or nerve cells in the absence of an esterase inhibitor. With eserine present, labelled acetylcholine was taken up uniformly by muscle segments; when eserine was then removed, radioactive acetylcholine remained only near neuromuscular junctions.
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PMID:Synthesis, storage and release of [14C]acetylcholine in isolated rat diaphragm muscles. 549 53

1. The exchanges of potassium and various other substances have been measured in beating frog's ventricles, using both superfused and distended preparations. In both preparations the high fluid flow rates used (1 ml./sec) cleared the ventricular cavity with a half-time (T(1/2)) of about 130 msec.2. Histological sections show that the modal strand radius in the relaxed or contracted distended ventricle is 17.5 mu, and in the relaxed and contracted superfused ventricle is 17.5 and 27.5 mu respectively.3. In quiescent ventricles the resting potassium influx and efflux are approximately equal at about 16 p-mole/cm(2).sec. This figure is computed from Niedergerke's (1963b) estimate of a cell size of 3.5 mu taken from electron-micrographs. If the older figure of 9.2 mu from single isolated cells is used (Skramlik, 1921) then the fluxes are about 44 p-mole/cm(2).sec. To allow for some cell damage in these preparations a further increase in flux of about 30% may be necessary.4. Contraction leads to a diminution of both potassium influx and efflux. Measurements made at 100 msec intervals throughout the cardiac cycle have demonstrated (a) that this decreased K efflux occurs at the same time as the mechanical twitch, and (b) that the size of the decrease is dependent on the external calcium concentration. Other experiments show that a similar decrease can be obtained by inducing a contracture at a constant membrane potential. It is concluded that the decreased K efflux during contraction is due to mechanical distortion of the tissue. This leads to a further slowing of the K diffusion and allows considerable reabsorption of K to occur into the cells.5. Efflux analysis suggests that normal K diffusion in the extracellular space may be about 1/10 of that in free solution. If this is correct the true membrane fluxes may be x 5 those measured.6. Phasic efflux measurements of Na, Ca, K, Cl, SO(4), sorbitol and erythritol show that a peak of efflux occurs just after the point of maximum rate of contraction of the ventricle. The peak efflux of K is least but all the other substances show similar patterns. In calcium-free solutions these phasic changes are absent. It is concluded that these effects are mechanical.7. Net K and Na changes were measured in ventricles poisoned by ouabain. The computed net changes for quiescent ventricles were a gain of 2.8 p-mole/cm(2).sec of Na and a loss of 5.3 p-mole/cm(2).sec of K. On stimulation a further increase in Na uptake of 8 p-mole/cm(2) occurred with no further loss of potassium. These results are computed for a cell diameter of 3.5 mu, for the larger diameter of 9.2 mu appropriate values of Na and K are 7.4 and 13.4 p-mole/cm(2).sec respectively for quiescent ventricles and an extra Na uptake of 21 p-mole/cm(2) per action potential. These results: (a) show that no large degree of single-file interaction occurs on the K movements, (b) are in agreement with the hypothesis that the membrane K fluxes are underestimated and (c) show that sufficient Na enters the cells per action potential to discharge a capacity of about 4 muF/cm(2).8. A general conclusion reached in these experiments is that ion movements during the long cardiac action potential cannot easily be measured because of mechanical artifacts.
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PMID:The efflux of potassium, sodium, chloride, calcium and sulphate ions and of sorbitol and glycerol during the cardiac cycle in frog's ventricle. 565 77

Calcium accumulation by rod disks was studied in excised bullfrog retinas with 45Ca tracer-exchange methods. Ca uptake by disks is a necessary requirement if light-induced Ca releases from disks mediate photoreceptor excitation. In an hour-long incubation, disks exchanged less than or equal to 0.01 mole of Ca per mole of rhodopsin, or less than or equal to 10% of their total Ca. This corresponds to a unidirectional flux of less than or equal to 0.01 fmol/cm2 S, or less than or equal to 5 ions/disk-second across the disk membrane. Neither incubation in 10 mM Ca (which increases cytoplasmic activity 10--100-fold) nor photostimulation (which photoactivated up to 50% rhodopsin/h) had measurable effect on exchange rate, though an increase of several orders of magnitude would have been expected according to the hypothesis. The observed exchange could not be explained by: (a) 45Ca losses from disks before measurement (neither the net efflux nor the Ca-Ca exchange property of disks adequately explains such losses), (b) a limited pool of exchangeables Ca from strongly binding intradiskal sites, or (c) rate-limiting flux across the plasma membrane during incubation. For the study of the Ca efflux properties of disks, separate experiments were performed with 45Ca-loaded disks. Intradiskal activity could be estimated from the disks' hyperosmotically sensitive 45Ca pool and from their intradiskal volume (indirectly assayed by density). Ca-Ca exchange was undetectable (less than or equal to 0.1 fmol/cm2 S) in disks whose intradiskal activity was at least 0.3 mM. Net efflux was 0.2 fmol/cm2 S for an intradiskal activity of approximately 1 mM and is comparable to published fluxes for phospholipid vesicles. These results seem to exclude the internal space of disks as the source of Ca for photoreceptor excitation.
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PMID:Calcium flux across disk membranes. Studies with intact rod photoreceptors and purified disks. 625 76

1. Phospholipid vesicles reconstituted with Na-K-ATPase from pig kidney, show slow passive pump-mediated (86)Rb fluxes in the complete absence of ATP and phosphate.2. The Rb fluxes are inhibited in vesicles prepared from enzyme pre-treated with either ouabain or vanadate ions. Rb fluxes through Na-K pumps oriented inside-out or right-side out by comparison with the normal cellular orientation can be distinguished by effects of vanadate on one or both sides of the vesicle.3. (86)Rb uptake into Rb-loaded vesicles represents a (86)Rb-Rb exchange. The maximal rate of exchange through inside-out and right-side out oriented pumps is equal, suggesting a random arrangement of the pumps across the vesicle membrane. This Rb-Rb exchange is half-saturated on inside-out and right-side out pumps at about 0.6 and 0.2 mM-external Rb respectively.4. (86)Rb uptake into Rb-free vesicles represents a net Rb flux. The Rb uptake through inside-out pumps has a maximal rate about equal to the Rb-Rb exchange, half-saturates at an external Rb concentration of roughly 0.5 mM, and shows evidence for co-operativity. Net Rb uptake through right-side out pumps is very slow, and half-saturates at roughly 0.1 mM external Rb.5. K ions at low concentrations in the exterior medium stimulate (86)Rb uptake, but at high concentrations, inhibit. Na ions in the exterior medium always inhibit (86)Rb uptake. The result suggests that K ions are transported in co-operative fashion together with Rb ions, while Na ions block the Rb fluxes.6. The presence of Rb congeners at the vesicle interior raises the (86)Rb uptake through inside-out pumps with the decreasing order of effectiveness: Li > Na > Cs > K > Rb. Stimulation by Na ions involves a Rb-Na exchange.7. Turnover numbers were estimated from parallel measurement of Na/K pump mediated fluxes and amount of covalent phosphoenzyme. In units of moles of ion per mole of phosphoenzyme per second at 20 degrees C the following values were obtained: ATP-dependent Na-Rb exchange, 43; (ATP+phosphate)-stimulated Rb-Rb exchange, 7. For (ATP+phosphate)-independent fluxes: Rb-Rb exchange 0.25; net Rb uptake 0.15 and Rb-Na exchange 0.65.8. Mg ions in the exterior medium inhibited both net and exchange Rb fluxes through inside-out pumps in a manner antagonistic with respect to Rb. Mg and vanadate ions inhibit the Rb fluxes in a synergistic fashion.9. The results are interpreted in terms of a model in which net and exchange (86)Rb fluxes occur via conformational transitions between form E(1) which binds Rb at the cytoplasmic face of the protein, the form E(2) (Rb)(occ) containing occluded Rb ions and a form E(2) which binds Rb at the extracellular face of the protein. A kinetic analysis allows us to identify rate-limiting steps of the transport cycle by making use of our transport data in combination with values of rate-constants for conformational transitions observed directly in isolated Na-K-ATPase.
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PMID:Passive rubidium fluxes mediated by Na-K-ATPase reconstituted into phospholipid vesicles when ATP- and phosphate-free. 629 Jun 46

The mammalian small intestine is extensively innervated by cholinergic nerve fibers, including projections to the muscular and submucosal layers. This study tested the hypothesis that cholinergic agents modulate ileal transport independent of alterations in intestinal vascular resistance and motility. Ten-centimeter segments of rabbit ileum (n = 32) were vascularly perfused ex vivo with a physiologic electrolyte solution containing red cells. The lumen was perfused with an electrolyte solution containing [14C]polyethylene glycol. Net fluxes of water, sodium, and chloride were calculated during three 20-min periods: basal, drug infusion, and recovery. Agents infused at a final arterial concentration of 10(-5) mole/liter included acetylcholine, atropine, and hexamethonium. Measured perfusion pressure reflected changes in vascular resistance. Recovery calculations controlled for motility effects. Acetylcholine caused significant secretion of water, sodium, and chloride (P < 0.05). The infusion of atropine or hexamethonium alone had no effect. Atropine but not hexamethonium prevented the prosecretory effect of acetylcholine. There were no significant changes in perfusion pressure or 14C recovery for any infused agent. Acetylcholine-induced ileal secretion is (1) mediated via atropine-sensitive muscarinic cholinergic receptors, (2) independent of extraintestinal neural pathways, and (3) independent of changes in vascular resistance or motility. These data support the hypothesis that acetylcholine influences ileal transport directly, independent of alterations in vascular resistance and motility.
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PMID:Cholinergic agents modulate transport in the isolated, perfused ileum. 853 65


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