Renal magnesium handling and its hormonal control

1994 ◽  
Vol 74 (2) ◽  
pp. 305-322 ◽  
Author(s):  
C. de Rouffignac ◽  
G. Quamme

Our understanding of renal Mg handling has been expanded in recent years with the use of electron probe, ultramicroanalysis, and fluorescent dye techniques to determine total Mg and free Mg2+ in individual tubule segments and cells, respectively. Recent studies have shown that [Mg2+]i is a highly mobile cation that may be altered by a number of influences including hormones. It is likely that the hormonal changes in [Mg2+]i, reported here and elsewhere, are involved in intracellular metabolism and regulation rather than transepithelial transport. The role of intracellular Mg2+ in control of cell function is poorly understood. However, it is evident that [Mg2+]i may be rapidly charged through a number of different influences that may have important effects on cell function. These kinds of data have enlarged our understanding of Mg conservation by the renal tubule but have posed many questions for further study. Magnesium is handled in different ways along the nephron. About 80% of the total plasma Mg (1.5-2.0 mM) is ultrafilterable across the glomerular membrane. Of the ultrafilterable Mg (1.2-1.6 mM), only 20-25% is reabsorbed by the proximal tubule, including the convoluted and straight portions. This is in contrast to Na and Ca reabsorption, which amounts to approximately 70 and 60%, respectively, in the proximal nephron. Accordingly, the fractional delivery of Mg to the thick ascending limb of the loop of Henle is much greater than that of Na or Ca. It is now evident from micropuncture studies that proportionally greater amounts of Mg (50-60%) are reabsorbed in the loop compared with Na (20-25%) or Ca (30-35%). Because the terminal nephron segments, including the DCT and collecting tubule, reabsorb only a small portion of the filtered Mg (approximately 5%), the loop of Henle plays a major role in the determination of Mg reabsorption, and it is in this segment that the major regulatory factors act to maintain Mg balance. Magnesium reabsorption in the thick ascending limb takes place in the cortical segments, at least in the mouse and rat. Evidence summarized here suggests that Mg is passively reabsorbed via the paracellular pathway in the cTAL of the loop of Henle. Several factors affect Mg reabsorption in the loop of Henle. Hypermagnesemia and hypercalcemia inhibit reabsorption leading to increased urinary excretion of Mg and Ca. These effects have been reviewed in detail elsewhere (113, 149). Magnesium depletion, for instance through dietary Mg deprivation, enhances Mg reabsorption in the loop of Henle before the fall in plasma Mg concentration and filtered Mg load.(ABSTRACT TRUNCATED AT 400 WORDS)

2014 ◽  
Vol 63 (4) ◽  
pp. 22-33 ◽  
Author(s):  
Irina Aleksandrovna Gaziyeva ◽  
Guzel Nukhovna Chistyakova ◽  
Irina Ivanovna Remizova

The Purpose. To study the role of hormonal and vascular dysregulation for the genesis of early reproductive losses without fetus chromosomal abnormalities. Materials and methods. The study involved 150 pregnant women: 38 women with early reproductive losses in this pregnancy (main group) and 112 women with delivery of live full-term infant (comparison group). Determination of factors characterizing the function of fetoplacental complex, indicators of the endothelial function and regulators of angiogenesis was performed in the first trimester of progressive pregnancy. Results. It is established that the mechanisms of abortion in the first trimester is associated with reduced production of hormones and proteins, which are indicators of the formation and function of fetoplacental complex and mediating immunomodulatory, tolerogens and angiogenic effects: β-HCG, PAPP-A and trophoblastic β-1-glycoprotein. Impair of hormonal control of gestational remodeling of the maternal body is associated with endothelial dysfunction and dysregulation of angiogenesis. Markers of endotheliopathy are: increased levels of endothelin-1, propeptide big-endothelin and homocysteine, decreased production of total and endogenous nitrite, and the changing of release of soluble adhesion molecules. Disbalans of stimulators and inhibitors of angiogenesis is characterized by the increased level of proangiogenic vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) as well as by the reduction of level of antiangiogenic soluble receptor of VEGF (sVEGF-R1), protein 1, binding insulin-like growth factor (IGF-BP1), and placental growth factor (PlGF). Conclusion. The determination of factors of hormonal and vascular dysregulation in the early pregnancy contributes to the timely identification of women with risk of miscarriage.


1984 ◽  
Vol 246 (2) ◽  
pp. F213-F220 ◽  
Author(s):  
J. M. Elalouf ◽  
N. Roinel ◽  
C. de Rouffignac

The effects of physiological doses of human calcitonin (HCT) on renal excretion and tubular transport of water and electrolytes were investigated in hormone-deprived rats, i.e., homozygous DI Brattleboro rats with reduced levels of circulating glucagon, parathyroid hormone, and thyrocalcitonin, as these hormones are believed, together with ADH, to stimulate the same cells of the thick ascending limb. The experimental design was similar to the one used in a preceding study aimed at determining the effects of ADH in hormone-deprived rats [C. de Rouffignac et al. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F156-F164, 1983]. In the present experiments, HCT consistently increased the reabsorption of Mg, Ca, and K and, to a lesser extent, Na and Cl in the loop of Henle, but phosphate transport did not rise. The urinary excretion rate of Mg and Ca fell significantly. These data are very similar to the findings obtained with ADH on hormone-deprived rats. It is concluded that, in vivo, administration of HCT 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, and 2) consistently enhances Mg and Ca reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle. The similarity of the physiological responses elicited by ADH and calcitonin on the thick ascending limb supports the hypothesis of multiple hormonal control of electrolyte transport by the thick ascending limb.


1972 ◽  
Vol 43 (5) ◽  
pp. 597-603 ◽  
Author(s):  
J. L. Day ◽  
M. Knight ◽  
J. R. Condon

1. A reliable, reproducible and specific method for determination of pancreatic glucagon in plasma by radioimmunoassay is described and plasma glucagon was measured in normal subjects and patients with acute pancreatitis. 2. In patients with acute pancreatitis the normal relationship between glucagon and glucose was impaired and disturbance of alpha-cell function was indicated by relative hyperglucagonaemia in patients with moderately severe disease. 3. In patients with severe pancreatitis glucagon concentrations were low and the possible relationship between hyper- and hypo-glucagonaemia and the pathogenesis of acute pancreatitis is discussed. 4. Insulin values in acute pancreatitis, although increased, were not as high as would be expected for the raised glucose concentrations. 5. It is concluded that both alpha- and beta-cell dysfunction may account for the high incidence of carbohydrate intolerance in acute pancreatitis.


Development ◽  
1953 ◽  
Vol 1 (3) ◽  
pp. 269-277
Author(s):  
V. B. Wigglesworth

I Propose to consider two kinds of determination and differentiation which have been studied in the hemipteron Rhodnius prolixus. (i) The determination of the cell or group of cells, with their subsequent differentiation to produce a given part of the body, (ii) The determination or control of the characters of that part—whether these are to be juvenile (larval) or adult (imaginal). Discussion of this second type of determination will require consideration of the role of hormones in controlling differentiation in insects. The integument of the abdomen in the Rhodnius larva consists of a single layer of epidermal cells and the overlying cuticle. At regular intervals the cuticle is modified to form little plaques each of which bears an innervated bristle (Wigglesworth, 1933). The cuticle is pierced at intervals by the ducts of dermal glands: these form a cluster of 4 or 5 around each plaque, with occasional single glands in the clear space between (Wigglesworth, 1947) (Fig. 3, A).


1996 ◽  
Vol 271 (4) ◽  
pp. F831-F845 ◽  
Author(s):  
J. Kim ◽  
G. S. Lee ◽  
C. C. Tisher ◽  
K. M. Madsen

At birth, the rat renal papilla has the structural composition of the mature inner stripe of the outer medulla. All loops of Henle have the configuration of short loops, and there are no ascending thin limbs. This study examines the role of apoptosis in the differentiation of the loop of Henle and the development of the ascending thin limb in the rat kidney. Kidneys of 20-day-old fetuses and 1-, 3-, 5-, 7-, 14-, and 21-day-old pups were preserved for immunohistochemistry and electron microscopy. Using a preembedding immunoperoxidase method, we identified thick ascending limbs by labeling with antibodies to the serotonin receptor, 5-HT1A, and descending thin limbs were identified by labeling with antibodies to aquaporin-1. Three methods were used to identify apoptotic cells as follows: 1) in situ nick end labeling using the ApopTag kit, 2) toluidine blue staining on plastic sections followed by etching, and 3) transmission electron microscopy. At birth, tubules with 5-HT1A immunoreactivity were present throughout the renal papilla, and there were no ascending thin limbs. From 1 to 14 days of age, staining for apoptosis was observed in numerous cells in the 5-HT1A-positive epithelium, beginning at the papillary tip and ascending to the border between outer and inner medulla. This was associated with transformation from a cuboidal to a squamous epithelium and subsequent disappearance of 5-HT1A immunostaining from the transformed cells. Electron microscopy confirmed the presence of apoptotic cells and phagocytosed apoptotic bodies in the thick ascending limb in the renal papilla. We conclude that the ascending thin limb is derived from the 5-HT1A-positive thick ascending limb by apoptotic deletion of thick ascending limb cells and transformation of the remaining tubule cells into the 5-HT1A-negative ascending thin limb.


2010 ◽  
Vol 299 (6) ◽  
pp. F1396-F1400 ◽  
Author(s):  
Pablo D. Cabral ◽  
Guillermo B. Silva ◽  
Sandra T. Baigorria ◽  
Luis A. Juncos ◽  
Luis I. Juncos ◽  
...  

Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2α (8-iso-PGF2α) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2α regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2α increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2α on NaCl transport by measuring chloride absorption ( JCl) in isolated microperfused cTALs. Adding 8-iso-PGF2α to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min−1·mm−1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min−1·mm−1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min−1·mm−1, and 8-iso-PGF2α raised it to 35.1 ± 1.4 fmol·min−1·mm−1, an increase of 94% ( P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 μM), 8-iso-PGF2α failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min−1·mm−1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min−1·mm−1; NS). We concluded that 8-iso-PGF2α stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.


2019 ◽  
Vol 35 (10) ◽  
pp. 1815-1824 ◽  
Author(s):  
Martine T. P. Besouw ◽  
Robert Kleta ◽  
Detlef Bockenhauer

Abstract Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.


Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
S Barkha ◽  
M Gegg ◽  
H Lickert ◽  
M Königshoff

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.


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