摘要:

To ascertain possible interactions of intracellular Mg2+ and Ca2+, the concentration of intracellular free Ca2+ ([Ca2+]i) and intracellular free Mg2+ ([Mg2+]i) were experimentally increased within physiological ranges and it was measured by means of fura-2 and mag-fura-2 whether the increased concentration of one divalent cation affected the concentration of the other. A four-fold increase of [Ca2+]i in rat thymocytes by concanavalin A or thapsigargin had no significant effect on [Mg2+]i. Incubation of rat thymocytes in Na+-free medium increased [Mg2+]i from 0.35 to 0.7 mM. This increase in [Mg2+]i did not affect [Ca2+]i or the action of thapsigargin on [Ca2+]i.

ISSN:1420-4096    

DOI:10.1159/000173842

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Immunoglobulin light chains, β2-microglobulin, insulin, and lysozyme are low-molecular-weight proteins (LMWP) shown to bind to renal brush border membranes. Competition among these proteins and the role of electrical charge in binding to brush border membranes have not been resolved. To investigate these factors, we performed displacement experiments with [125I]-labeled β2-microglobulin (pI - 5.6) using six species of LMWP over a pi range of 4.4-11.0. The inhibition constants, Ki, of these six competing ligands, χ- and λ-light chains, lysozyme, insulin, cytochrome c, and myoglobin, determined from the log displacement curves, ranged from 4×10-5 to 8×10-4M. These experiments show marked cross-competition among LMWP for binding to brush border membranes. There was no correlation between Ki and pI indicating that the molecular structure is a more important determinant of LMWP binding to brush border membranes than net electrical c

ISSN:1420-4096    

DOI:10.1159/000173844

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 µM λ- or χ-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the λ-and ĸ-light chains on phosphate transport were similar, 34 and 35 µM respectively. The IC50 of the ĸ-light chain on glucose transport was 360 µM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.0l for the λ-light chain and r = 0.93, p < 0.001 for the χ-light chain, on phosphate transport; and r = 0.93, p < 0.00l for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompet-itive inhibition. The inhibition constant 89 µMfor phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain neph

ISSN:1420-4096    

DOI:10.1159/000173861

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The luminal membrane of collecting duct cells, especially the intercalated cells, is normally exposed to active kallikrein. This is the consequence of the specific localization of this renal enzyme in the connecting tubule cells and its principal route of secretion being into the tubular lumen. It is conceivable that kallikrein acts downstream on a transporter involved in distal bicarbonate handling. To investigate this possibility, we estimated bicarbonate concentration and measured kallikrein amidolytic activity in urine fractions collected after a classical stop-flow experiment in rabbits. A highly significant inverse correlation was found between these parameters (r = -0.94, p < 0.001) in the peak kallikrein fractions. Neither sodium nor potassium concentration were correlated to kallikrein. This suggests that the physiological role of renal kallikrein may be to regulate extracellular fluid pH by inhibiting collecting duct bicarbonate secretion. To test the hypothesis that tubular fluid kallikrein activity and bicarbonate secretion are causally related, we developed a novel in vivo stop-flow injection model (‘orthograde stop-flow’). A hog-kallikrein containing solution (0.5 µg/ml) was injected through the abdominal aorta into the renal tubular system of one kidney of barbiturate-anesthetized rats, while the renal blood supply was interrupted. The ureter was then occluded and renal blood perfusion reinitiated. After a 2-min contact time five 125-µl urine fractions were collected. Bicarbonate secretion was clearly detected in the second and third fractions (i.e. those coming from the collecting ducts) of the control animals, which had received only the vehicle. There was no bicarbonate secretion peak in the corresponding urine fractions collected from kallikrein-injected animals. We conclude that intraluminal kallikrein inhibits collecting duct bicarbonate secretion, probably by inhibiting the chloride/bicarbonate exchanger of β-intercalated

ISSN:1420-4096    

DOI:10.1159/000173862

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Hippurate is known to be synthesized from benzoate and glycine in the liver and kidney. It takes part in renal ammoniagenesis by modulating the activity of γ-glutamyl transpeptidase (γGT). Due to its chemical structure, however, hippurate might also serve as a substrate of renal ammoniagenesis. Hippurate may yield ammonia either having been cleaved by hippuricase or by Erlenmeyer’s reaction after condensation with an aldehyde. In order to elucidate the possibility of hippurate being a substrate of renal ammoniagenesis, experiments were carried out on cortical kidney slices and on isolated tubular segments of the rat. The incubation medium (pH 7.1) was enriched with 10 mmol/l hippurate spiked with l5N-hippurate, some of the known competitive inhibitors of hippuricase, acivicin and different aldehydes. Factors known to affect hippuricase or γGT did not interfere with renal ammonia production. Glyceraldehyde (up to 1.0 mmol/l) but not glycerate had a stimulating effect, especially on the ammoniagenesis from hippurate. In normal rats fed a vegetarian diet, 1% of the added 15N moiety was found to be 15NH3. Renal l5NH3 production was significantly greater if, prior to the experiments, the animals were either acidotic or had a reduced renal mass or were fed animal proteins. These results indicate that hippurate may, to a certain extent, serve as substrate for ammoniagen

ISSN:1420-4096    

DOI:10.1159/000173863

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The steady state levels of mRNA encoding for metalloproteinase (MMP)-l -2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 were examined in glomeruli at 4,12, and 24 weeks after the injection of streptozocin (STZ) in rats. The mRNA levels for MMP-1 and MMP-3 decreased with age in STZ-induced diabetes. At 24 weeks after STZ injection, mRNA levels for MMP-1 and MMP-3 fell to 40% (p < 0.01) and 20% (p < 0.01), respectively, in the glomeruli of diabetic rats when compared with control rats. In contrast, mRNA levels for TIMP-1 increased significantly with age in the diabetic glomeruli and reached an 8-fold (p < 0.01) increase at 24 weeks after STZ injection. mRNA levels for MMP-2 were not altered in glomeruli from diabetic and control rats throughout the experimental period, whereas those for MMP-9 were not detected in glomeruli from either group of rats. Insulin treatment partially ameliorated the decrease in mRNA levels for MMP-1 and MMP-3 and the increase in those for TIMP-1 in the glomeruli of diabetic rats. These data indicate that abnormal gene regulation of MMPs and TIMP-1 in the glomeruli of diabetic rats may contribute to the progression of glomerular lesions and that hyperglycemia or insulin deficiency may be associated with abnormal MMPs and TIMP-1 gene regulation.

ISSN:1420-4096    

DOI:10.1159/000173864

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Multifrequency bioelectrical impedance was used to predict changes in body water compartments during renal dialysis. Weight loss during dialysis was assumed to be water loss. Predicted total body water (TBW) from impedance after dialysis did not differ significantly from TBW determined by deuterium oxide dilution. However, the predicted change in TBW from bioelectrical impedance largely exceeded the observed weight (water) loss. The predicted change in extracellular water was slightly but significantly lower compared to the observed weight loss. The ratio of impedance at 1-100 kHz increased in all subjects during dialysis, and may be a simple tool to assess body water distribution.

ISSN:1420-4096    

DOI:10.1159/000173865

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173866

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173867

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173868

出版商:S. Karger AG    

年代:1994

数据来源: Karger