Functional asymmetry in phosphate transport and its regulation in opossum kidney cells: parathyroid hormone inhibition

The sidedness (apical vs basolateral) of the inhibitory of phosphate (P_i) transport by parathyroid hormone (PTH) was investigated in opossum kidney (OK)-cell monolayers grown on permeant support. PTH was found to regulate the activity of only the apical Na/P_i cotransporter, having no effect on the basolateral transport systems. Transport inhibition was approximately 100-fold more sensitive to apical PTH application (K _d: 5×10^–12 M) than to basolateral application (K _d: 5×10^–10 M). The time-course of the inhibitory response was identical from the two cell surfaces, with half-maximum inhibition occurring at about 20 min and almost full inhibition by 90 min. Experiments on diffusion and degradation demonstrated that the difference in K _d at the two cell surfaces was not due to differential metabolism or diffusion. Tests of cooperativity between the apical and basolateral regulatory events at intermediate concentrations suggested that the presence of PTH on one side of the monolayer reduced the scope of response from the other side. At maximum doses of PTH (10^–7–10^–8 M) the transport inhibition from either side was equal and not additive. We conclude that in OK-cell monolayers grown on permeant support only apical Na/ P_i co-transport is sensitive to PTH inhibition and that PTH receptor properties may be different on the apical and basolateral surfaces.     

Functional asymmetry of phosphate transport and its regulation in opossum kidney cells: phosphate “adaptation”

The polarity (apical vs basolateral cell surface) of the up-regulatory response (adaptation) to low medium phosphate (P_i) concentration on apical and basolateral P_i transport systems was investigated in opossum kidney (OK) cell monolayers grown on permeant supports. Incubation of cultures in low-P_i medium, given either only to the apical or simultanously to the apical and basolateral compartments, increased the rate of transport of both the apical and the basolateral Na/P_i cotransport systems. The basolateral Na-independent, 4,4-diisothiocyanatostilbene-2, 2-disulphonic-acid-sensitive P_i transport system was unaffected by P_i deprivation. Incubation with low-P_i medium from only the basolateral side failed to elicit any adaptive response in P_i transport. When cells were P_i-limited either apically or on both sides for short periods of time, adaptation was apparent within 2 h and close to maximal by 6 h, and the alteration in P_i transport was consistant with an increase in J _max for both the apical and basolateral Na/P_i cotransport systems. These data suggest that apical Na-dependent P_i influx is important in signalling the adaptive response to low extracellular P_i.     

Effect of glucagon on magnesium renal reabsorption in the rat

The recent localization, in the rat, of a glucagon-sensitive adenylate cyclase in these segments where the bulk of calcium and magnesium is reabsorbed suggests an effect of this hormone on calcium and magnesium tubular transport. Renal tubular handling of calcium and magnesium as well as of sodium and phosphate was therefore studied by clearance methods in anesthetized rats, either intact or thyroparathyroidectomized (TPTX), infused with glucagon at a rate of 25 ng·min^–1/100 g bw just after a priming dose of 2.5 g. The hormone administration resulted in a significant decrease of absolute and fractional magnesium excretion (from 16.3±0.7% to 9.7±1.7% for intact rats and from 20.9±1.8% to 6.9±1.0% for TPTX rats), associated with the well-known increase in sodium and phosphate fractional excretion. Moreover, a small and transient decrease of calcium fractional excretion was observed concomitantly with a decrease of plasma calcium concentration. The significant increase in magnesium absolute reabsorption, observed whatever the filtered load and independently of PTH and calcitonin, may be an evidence for a direct tubular effect of glucagon.     

Simultaneous Mg,Ca, P,K, Na and Cl analysis in rat tubular fluid

Summary The micropuncture recollection technique was used for further analysis of Mg, Ca, P, Na, Cl and K tubular handling during and after acute magnesium plasma loading in the rat. The concentrations of these different ion species in late proximal and early distal fluid samples, ureteral urine and plasma ultrafiltrates were measured using electron probe microanalysis.³H-inulin was used as glomerular indicator.The results indicate that 1, late proximal (TF/P_f)Mg/In values remained proportional to the filtered load (about 80%); 2. part of the filtered Mg was reabsorbed in the loop of Henle by an active and saturable transport mechanism; 3. early distal (TF/P_f)Mg/In values during and after Mg loading were below the corresponding (U/P_f)Mg/In values; this observation might either indicate net Mg tubular excretion by the terminal nephron segments or result from the building up of a medullary Mg ion pool during the loading period; 4. acute hypermagnesemia induced transient calciuria, shown to result from decreased Ca reabsorption in the terminal segments; 5. it enhanced P reabsorption in the terminal segments; the drop in P excretion might have been mediated by decreased PTH release; 6. tubular handling of the other ion species was relatively unaffected by increasing tubular Mg loading.     

Calcium carbonate as a phosphate binder in dialysis patients: Evaluation of an enteric-coated preparation and effect of additional aluminium hydroxide on hyperaluminaemia

Summary Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure; however, a high frequency of hypercalcaemia has been reported. To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect, we conducted a double-blind, crossover trial in 21 patients undergoing chronic haemodialysis. Aluminium hydroxide therapy was replaced with calcium carbonate. The subjects then randomly received either an enteric-coated or a gastric-coated preparation. Calcium carbonate (3.1–3.6 g/d) controlled serum phosphate concentrations as effectively as aluminium hydroxide (2.9 g/d). Concurrently, there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin, the latter suggesting a decrease in bone turnover. Overall, hypercalcaemic episodes developed in 9 patients (43%) and occurred at a considerable frequency (33 episodes per 100 patient-months) during treatment with the gastric-coated formulation. Following conversion to enteric-coated calcium carbonate (3.6 g/d) patients had fewer occurrences of hypercalcaemia (12 episodes per 100 patient-months,P<0.05) and, as compared to the gastric-coated preparation, increases in serum calcium >3.00 mmol/l were not observed at all. Hyperaluminaemia was regressive during therapy with calcium carbonate, but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine, indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium.We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients. However, undesirable hypercalcaemic episodes may occur, the frequency and severity of which can be lowered by the use of an enteric-coated preparation. Concomitant use of aluminium hydroxide and calcium carbonate should be restricted to patients in whom the degree of aluminium accumulation is monitored by serial desferrioxamine tests.     

Phosphate transfer and tubular pH during renal stopped flow microperfusion experiments in the rat

Summary The loss of³²P-phosphate salts by the luminal compartment of cortical tubules was studied in control and in acetazolamide-infused rats, during stopped-flow microperfusion with 100 mM phosphateraffinose solutions. When the initial pH of the perfusion solution was low (5.5), phosphate was lost more rapidly from proximal tubules than at high initial pH (8.2). The average half-time of phosphate loss was 31.9 s during acid, and 66.0 s during alkaline perfusion in proximal tubules of control rats; in acetazolamide-infused rats half-times were 77.0 and 86.6 s for acid and alkaline perfusions. Thus acetazolamide infusion slows the rate of phosphate loss by proximal tubules, when the perfusion solution is acid, but has no significant effect if its pH is alkaline. These half-times compare to proximal acidification rates of 7.43 s in control and 13.2 s in acetazolamide-infused rats. In distal tubules of control rats no significant loss of phosphate was observed during the period of perfusion. It is concluded that the loss of phosphate, in proximal tubules, is markedly slower than the changes in tubular pH and so its effect on tubular acidification must be of minor importance. In distal tubules changes in pH are not due to transepithelial phosphate movement.Supported by Fund. de Amparo à Pesquisa do Estado de São Paulo     

宣肺止嗽合剂中4种生物碱的含量测定方法研究

目的:建立同时测定宣肺止嗽合剂中4种生物碱含量的高效液相色谱分析方法。方法:色谱柱为安捷伦SB-C₁₈(250 mm×4.6 mm, 5μm);流动相：乙睛-0.1%磷酸溶液(3∶97);检测波长：210 nm;流速：1.0 mL·min^-1;柱温：30℃;进样量：10μL。结果:吗啡、磷酸可待因、蒂巴因、盐酸罂粟碱4种生物碱成分在各自的质量浓度范围内线性关系良好,相关系数r²≥0.9960,平均回收率分别为97.8%、96.9%、97.4%、97.5%,对应的RSD分别为1.2%、1.2%、1.6%、1.4%(n=9)。10批宣肺止嗽合剂样品中吗啡的含量为0.078～0.160 mg·mL^-1、磷酸可待因的含量为0.008～0.025 mg·mL^-1、蒂巴因的含量为0.0002～0.0013 mg·mL^-1、盐酸罂粟碱的含量为0.010～0.025 mg·mL^-1。结论:该方法操作简便,结果准确,可用于宣肺止嗽合剂的质量控制,为其质...     

FGF23 in hemodialysis patients is associated with left ventricular hypertrophy and reduced ejection fraction

Background

Fibroblast growth factor 23 (FGF23) is known to cause left ventricular hypertrophy (LVH), but controversy exists concerning its effect in dialysis. This study evaluated associations between FGF23 levels, echocardiography and prognosis in patients on hemodialysis (HD).