J.-P. Bonjour

Adaptation of phosphate transport to low phosphate diet in renal and intestinal brush border membrane vesicles: influence of sodium and pH.

The possible role of changes in the sodium (Na) affinity of the carrier for inorganic phosphate (Pi) in the adaptation of Pi transport to low Pi diet was examined in both renal and intestinal brush border membranes vesicles (BBMV) obtained from the same animal. This role was assessed by measuring the Na concentration resulting in half maximal activation of Pi transport (K0.5Na) in renal and intestinal BBMV prepared from animals adapted to either low (LPD) or high (HPD) phosphorus diet for 7 days. TheK0.5Na was not modified by dietary Pi, in both renal and intestinal BBMV. LPD increased maximal Pi transport from 1794.8±198.0 to 296.4±362.0 in renal and from 28.2±3.4 to 80.5±7.2 pmol/mg 10 s in intestinal BBMV. For both LPD and HPD lowering pH from 7.4 to 6 dramatically increasedK0.5 Na in renal and intestinal BBMV. As compared to pH 7.4, it was enhanced by approximately 200% in both renal and intestinal membranes. This change of Na affinity with acidic pH prevented the expression of Pi transport adaptation at 100 mM Na concentration. However, at saturating Na concentrations (500 mM for renal, 300 mM for intestinal membranes), Pi transport adaptation was equally expressed at pH 6 and 7.4 in both types of membranes. Hill coefficient analysis indicates a 2:1 stoichiometry of Na to Pi in renal and intestinal membranes isolated from high or low Pi diet animals. This ratio was not modified by changes of the medium pH.

Effect of Absorbable and Nonabsorbable Sugars on Intestinal Calcium Absorption in Humans

The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with 99mTc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

Tumoral synthetic parathyroid hormone related peptide inhibits amiloride-sensitive sodium transport in cultured renal epithelia

The amino-terminal fragment of a tumoral parathyroid hormone-related peptide (PTHrP (1–34)) produced by a human squamous cell carcinoma of the lung was recently synthetized. In the present work its effect on the amiloride-sensitive sodium transport, taken as an estimate of the Na+/H+ exchanger activity of cultured opossum kidney (OK) epithelia was compared to that of synthetic bovine parathyroid hormone (bPTH (1–34)). Both PTHrP (1–34) and bPTH (1–34) inhibited the initial rate of amiloride-sensitive22Na transport. Half maximal inhibitory activity was obtained at about 10−11 M for both PTHrP (1–34) and bPTH (1–34). In conclusion, tumoral PTHrP (1–34) appears to be as effective as bPTH (1–34) for inhibiting the amiloride-sensitive Na transport, and presumably for decreasing the activity of the Na+/H+ exchanger present in the apical membrane of kidney epithelial cells.

The Adaptive System of the Tubular Transport of Phosphate

The present report is an attempt to review the state of our knowledge concerning the adaptation of the tubular transport of Pi in relation with the homeostasis of Pi.

Mechanism of Phosphate Transport Adaptation in Rat Intestinal and Renal Brush Border Membranes

Studies on the regulation of phosphate (Pi) transport in gut and kidney have revealed an adaptation of Pi transport under dietary restriction of Pi. In response to low Pi diet, Pi absorption is enhanced in kidney and small intestine (1,2). In kidney, this stimulation results, at least in part, from the increase in the capacity of the sodium-Pi cotransport process located in the brush border membrane of the proximal tubule. The Km of the transport process is not modified (3). It is not known, to the best of our knowledge, whether the adaptation of Pi absorption in small intestine is expressed at the brush border membrane level and how these changes occur, if any. Furthermore, since sodium is cotransported with phosphate in the luminal membrane of renal and intestinal tissues, it could be that an alteration of the dependency of the phosphate carrier on sodium played some role in the stimulation of Pi transport.

Renal Pi Transport in Young Growing and Adult Rats: Comparative Studies in Brush Border Membrane Vesicles (BBMV) and in Whole Kidney

The question where and how the renal transport of inorganic phosphate (Pi) is regulated has been the subject of numerous investigations over the last few years. In this regard, the discovery of a sodium-dependent Pi transport system in the brush border membranes of the renal cortex (1) has been of particular interest. It gave rise to the question of whether the Pi transfer rate determined by this system across the luminal membrane of the proximal tubule would be the only limited and regulated step of the overall net tubular Pi reab-sorption. Therefore we have been particularly interested in studying the relationship between alterations in the overall tubular Pi reabsorptive capacity and changes in the Pi transport at the level of brush border membrane vesicles (BBMV) of the renal cortex of rats. In this investigation the alterations in the renal handling of Pi were provoked by variation in dietary Pi, removal of the parathyroid gland, chronic administration of either 1,25-dihydroxyvitamin D to thyroparathyroidectomized animals or the diphosphonate ethane-1-hydroxy-1,1-diphosphonate (2,3).

Lait et santé osseuse : rôle essentiel du calcium et des protéines

Resume La nutrition contribue de facon majeure au developpement et au maintien d’une structure osseuse adaptee a resister aux contraintes mecaniques usuelles et donc, a la prevention des fractures osteoporotiques. L’effet positif des apports calciques et vitaminique D sur la sante osseuse tout au long de la vie est aujourd’hui largement admis sur la base des donnees experimentales precliniques et cliniques, ces dernieres incluant a la fois des etudes d’observation et d’intervention. Les proteines representent un troisieme nutriment qui influence selectivement la production d’IGF-1 ( Insulin-like Growth Factor -1), facteur indispensable a l’acquisition et au maintien de la masse minerale osseuse. Une fois le statut en vitamine D adequat assure par source cutanee et/ou nutritionnelle, une alimentation fournissant tout au long de la vie les apports conseilles pour le couple calcium-proteines represente une mesure d’hygiene de vie essentielle contribuant positivement a la sante osseuse et a la reduction du risque de fractures osteoporotiques au cours de la deuxieme partie de la vie adulte.

Influence of Calcium and Calcium Regulating Hormones on Renal Compensatory Growth

Reduction in the renal mass is followed by a compensatory hypertrophy of the remaining kidney (1, 2). The search for the mechanism which triggers renal compensatory hypertrophy (RCH) has been the object of numerous investigations (1, 2). Despite intense efforts, the exact nature of the signal or signals which is/are implicated in the renal compensatory response have not yet been identified. Nevertheless, there is convincing evidence that RCH is triggered by an organ-specific humoral substance which is present in the plasma but may originate from the kidney itself (2, 6). The rate of compensatory growth has been shown to be influenced by various factors such as age (8), protein intake (9), and several hormones including growth hormone (10, 11), testosterone (12), thyroid hormone (13) and adrenal steroids (14). All these factors influence not only the “compensatory” growth but also the normal or “obligatory” growth of the kidney. Therefore, these factors appear to be rather unspecific since evidence has been obtained that RCH after unilateral nephrectomy is a growth phenomenon different from normal growth (15). An important feature which distinguishes the two phenomena is the fact that RCH is reversible, whereas normal growth is irreversible (15).

Regulation Mechanisms of the Renal Phosphate Handling in Renal Failure — What is the Role of PTH?

It has been known for a long time, that plasma inorganic phosphate (Pi) increases in renal failure. Since 1954 it has been realized that this increase occurs only at a glomerular filtration rate (GFR) below approximately 25 ml/min (1). Above this value plasma Pi remains constant in spite of a decrease in GFR and with an unchanged urinary Pi. As a consequence, fractional excretion (FE) will have to increase or conversely fractional tubular reabsorption (TRP%) must decrease (1).