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Biomedical subjects

B Kaissling

Publications and source records attributed to B Kaissling.

At least 91 records · Page 5Linked to original sources

Kallikrein (kininogenase) in the mouse nephron: effect of dietary potassium.

Kininogenase activity of kallikrein was measured in microdissected mouse nephron segments using kininogen from dog plasma and a radioimmunoassay for bradykinin. When single nephron segments were examined, results showed a large scatter. This was found to be due to heterogeneity of distal convoluted tubules (DCT) from different nephrons, since replicate measurements in pools of DCT structures did not show this degree of variation. Nearly 20% of activity was accessible to extracellular substrate when freshly dissected segments were incubated in isoosmotic media. Freezing and thawing which markedly releases activity of intracellular enzymes, did not significantly elevate kininogenase activity. On the other hand deoxycholate and trypsin treatment increased tubular kininogenase activity in an additive fashion. A detailed analysis of microdissected tubule fragments revealed that kallikrein is concentrated in late distal convoluted tubule before entering a branching point (connecting tubule). In contrast initial portions of distal convoluted tubules and cortical collecting tubules contained only little kallikrein activity. Potassium rich diet increased basal and total activity 5-fold, when compared to a potassium poor diet.

Animals↗

Light and electron microscopic changes in the kidney of Wistar rats following treatment with cyclosporine A.

The morphological changes found in kidneys of patients undergoing chronic Cyclosporine A (CSA) treatment could, despite of numerous attempts, not yet be reproduced in reliable experimental models. The purpose of the present investigation was to systematically scan the in vivo fixed kidneys in CSA treated Wistar rats at the light and electron microscopic level. The study revealed changes in the proximal tubules, i.e., inclusion bodies, vacuolization, microcalcifications and regeneration. Some glomeruli displayed a thickening of the parietal sheet of Bowman's capsule. At the electron microscopic level, individual necroses of myocytes in the tunica media of afferent arterioles were observed. Thus, at the ultrastructural level, the kidneys of CSA treated normotensive Wistar rats do reveal morphological changes similar to those occurring in man.

Animals↗

Cellular heterogeneity of the distal nephron and its relation to function.

The distal segments beyond the macula densa--distal convoluted tubule, connecting tubule, cortical collecting duct--display cellular heterogeneity. The four different cell types, namely the DCT cell, CNT cell, the principal cell and intercalated cell differ mainly by the pattern of membrane amplification and they reveal also qualitative differences as to some cytoplasmic proteins. Each of the four cell types adapts to chronic changes in electrolyte metabolism with structural alteration, concerning essentially the membrane area over which the active transport step of the cell proceeds, in DCT-, CNT- and P-cells the basolateral cell membrane with the Na-K-ATPase, in intercalated cells the luminal cell membrane with a H+ ATPase. Since each cell type responds only to specific conditions with changes in membrane area and associated transcellular transport activity, morphological studies can help to determine the specific role of each cell type in the regulation of renal electrolyte excretion. Such investigations demonstrated that besides mineralocorticoid hormones the transport capacity of certain cells should depend on the solute composition of tubular fluid. Thus, changes in the transport pattern specifically induced in only one segment alters also the transport patterns of segments downstream. Cellular heterogeneity seems to guarantee the optimal regulation of renal electrolyte excretion.

Animals↗

Structural adaptation of the distal convoluted tubule to prolonged furosemide treatment.

Rats were treated with furosemide, continuously applied by implanted minipumps, for 6 days. As compensation for the salt lost with the urine the animals drank large amounts of a salt solution ad libitum. This procedure resulted in an enlargement of kidney cortex. Light and electron microscopic studies revealed a proliferation of the distal convoluted tubule (DCT). The proportion of the DCT in the cortical tissue increased from 5.98 +/- 1.3% in controls to 9.54 +/- 1.7% (P less than 0.01) in treated rats. Basolateral cell membrane amplification in DCT cells increased from 17.33 +/- 2.9 to 38.24 +/- 5.8 (P less than 0.0001) in treated rats, while luminal membrane area per unit tubular length did not change. The structural changes after furosemide treatment in the DCT suggest an increase in active transcellular transport capacity of this segment. It is assumed that the chronically altered Na load of the tubular fluid (due to transport inhibition in the thick ascending limb of Henle's loop) delivered to the DCT may specifically stimulate the transport capacity of this segment by augmentation of basolateral cell membrane area. The changes occurring in the segment situated downstream to the one in which the function is impaired by furosemide emphasize the role of tubular fluid composition in the regulation of transport function.

Animals↗

Structural adaptation to altered electrolyte metabolism by cortical distal segments.

The four different renal cell types in the cortical segments beyond the macula densa--distal convoluted tubule (DCT) cell, the connecting tubule (CNT) cell, the principal (P) cell, and the intercalated (I) cell--each respond to prolonged specific stimuli with changes in cell membrane area. Increases in basolateral cell membrane area, reflecting the transport capacity of the cell, are associated in DCT cells with luminal, chronically high sodium load, in CNT cells with mineralocorticoids and tubular solute load, and in P cells with mineralocorticoids. In I cells the luminal cell membrane area seems to be influenced by the local luminal environment of the cells as well as by the peritubular environment. These structural findings indicate that tubular fluid composition as well as peritubular factors (e.g., mineralocorticoid levels) may have a role in regulating the transport capacity of distal cell types in the kidney.

Adaptation, Physiological↗

Distal tubular segments of the rabbit kidney after adaptation to altered Na- and K-intake. I. Structural changes.

The baso-lateral cell-membrane area in kidney tubules appears to be associated with the capacity for electrolyte transport; in the rabbit, it decreases from the distal convoluted tubule (DCT-cells) over the connecting tubule (CNT-cells) to the cortical collecting duct (principal cells). Adaptation to low Na-, high K-intake changes this pattern: CNT-cells at the beginning of the connecting tubule have the highest membrane area, which decreases along the segment, but remains two-fold higher than in controls. Principal cells have a four-fold higher membrane area than in controls. Simultaneous treatment with the antimineralocorticoid canrenoate-K inhibits the structural changes in CNT-cells only in end-portions of the connecting tubule and in principal cells. After prolonged high Na-, low K-intake DCT-cells display a two-fold higher membrane area than controls, while CNT-cells and principal cells are not affected. Simultaneous treatment with DOCA does not affect the DCT-cells but provokes a moderate increase in membrane area in CNT-cells, and a 5.5-fold increase in principal cells. The data provide evidence that DCT-, CNT- and principal cells are functionally different cell types. The baso-lateral cell-membrane area, associated with electrolyte-transport capacity, appears to be influenced in DCT-cells mainly by Na-intake, in CNT-cells mainly by K-intake and in part also by mineralocorticoids, and in principal cells mainly by mineralocorticoids.

Adaptation, Physiological↗

Distal tubular segments of the rabbit kidney after adaptation to altered Na- and K-intake. II. Changes in Na-K-ATPase activity.

Na-K-ATPase activity was measured in the convoluted part of the distal tubule (DCT), the connecting tubule (CNT) and the cortical collecting duct (CCD). The segments were microdissected from freeze-dried kidney tissue of rabbits adapted to various salt diets and exposed to large differences in endogenous and exogeneous mineralocorticoids. The Na-K-ATPase activity in the DCT is not influenced by mineralocorticoids. They do influence the activity in the CNT and in the CCD. In the CNT the highest activity was found with a low Na-, high K-diet. At the beginning of the CNT the enzyme activity is higher than in the end portion. While canrenoate-K treatment has no effect on Na-K-ATPase activity in the initial portions of the CNT, this drug decreases the Na-K-ATPase activity significantly in the end portion of the CNT. DOCA treatment has a significant effect on the enzyme activity in the CNT only in the end-portion of the segment, but provokes the highest Na-K-ATPase activity in the CCD. The changes in Na-K-ATPase are found to be associated with corresponding changes in the baso-lateral cell-membrane area in the segments affected.

Adaptation, Physiological↗

Three-dimensional shape of a Goormaghtigh cell and its contact with a granular cell in the rabbit kidney.

Goormaghtigh cells of the JGA are characterized by an extensive cellular ramification. In order to elucidate the shape and arrangement of the cell processes a three-dimensional model of a Goormaghtigh cell and of an adjacent granular cell has been constructed based on electron micrographs of a series of ultrathin sections. The model shows that a Goormaghtigh cell has the shape of a flatly pressed cylinder with both ends splitting up into a bunch of parallel processes. The processes maintain a close neighboring position and do not intermingle with processes of other Goormaghtigh cells. This feature is most puzzling when considering that Goormaghtigh cells and their processes are extensively connected by gap junctions. Even processes belonging to the same cell are electrically coupled with each other through gap junctions. The granular cells are clearly different in shape from Goormaghtigh cells. In granular cells bunches of processes are lacking. Granular cells obviously ramify into a few, large processes. The present findings are consistent with the assumption of a functionally central position of Goormaghtigh cells within the feedback mechanism of the JGA.

Animals↗

Binding of peanut lectin to specific epithelial cell types in kidney.

The binding of peanut agglutinin (PNA) to epithelial membranes of the rabbit kidney was evaluated at the light- and electron-microscope level using PNA conjugated to horseradish peroxidase. In the renal cortex and outer stripe of the medulla PNA appears to bind exclusively to the luminal membrane of intercalated cells in connecting tubules and collecting ducts. PNA also binds to the thin descending limb of the loop of Henle in the inner stripe and inner zone of the medulla. This very specific affinity of PNA should be useful in the isolation and characterization of specific cell types in cytologically heterogeneous epithelia.

Animals↗

Variability of intercellular spaces between macula densa cells: a transmission electron microscopic study in rabbits and rats.

The macula densa in rabbits and rats was studied by transmission electron microscopy (TEM). After different experimental procedures, the kidneys were fixed by direct perfusion with the fixative without prior flushing of the blood. With this technique, the renal cortex is consistently well preserved. The lateral intercellular spaces of all proximal and distal nephron segments were constantly found to be closed, whereas those of the macula densa varied: depending on the functional situation of the kidney, they were found to be either dilated or closed. Dilated intercellular spaces in the macula densa were encountered in control, sodium-rich, and sodium-deficient rabbits and rats and, in addition, in rats with hypotonic and isotonic hypervolemia. In contrast, in rats with hypertonic hypovolemia and in rats undergoing furosemide or mannitol diuresis, the lateral intercellular spaces of the macula densa were closed. Whether these findings reflect the in vivo state of the macula densa interspaces remains uncertain. The association with specific functional stages demonstrates, at least, a specific behavior of the macula densa cells that is different from that of all other proximal and distal nephron segments and appears to be similar to that of the collecting duct epithelium. The findings suggest that the macula densa is a water-permeable cell plaque within the otherwise water-impermeable thick ascending limb.

Animals↗

Ultrastructural organization of the transition from the distal nephron to the collecting duct in the desert rodent Psammomys obesus.

The transition from the nephron to the collecting duct is formed by three tubular segments (convoluted part of the distal tubule, connecting tubule, cortical collecting duct), which in the desert rodent, Psammomys obesus, transform gradually from one segment to the next, due to intermingling of their different cell types. The convoluted part of the distal tubule (DTC) starts abruptly, shortly beyond the macula densa and initially is homogeneously composed of characteristic DTC-cells. Subsequently, the DTC-cells intermingle with intercalated cells. The first appearance of the connecting-tubule cell, which gradually replaces the DTC-cell, is regarded as the beginning of the connecting tubule. The major portion of the connecting tubule is lined by connecting-tubule cells and intercalated cells. The first appearance of the principal cell between them defines the beginning of the cortical collecting duct, which in the medullary ray is lined by principal and intercalated cells only. Each cell type is described in detail and discussed in relation to the assumed function of the tubular segments. Interspecies differences in the cellular composition of the transitional zone from the nephron to the collecting duct are discussed in relation to the different organization of the collecting duct system.

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