ISSN:1420-4096    

DOI:10.1159/000173744

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173745

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173746

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The membrane surface of polarized epithelial cells can be divided in apical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton are involved in critical steps of both generation and maintenance of cell polarity. Generation of polarity is controlled by microtubules that serve as uniformly aligned and polarized cytoplasmic guiding structures for the vectorial and selective transport of Golgi-derived carrier vesicles to the apical cell surface. Targeting of membrane proteins to the basolateral cell surface does not depend on microtubules but follows the constitutive bulk flow of membranes. Once inserted into the lipid bilayer several membrane proteins such as the kidney anion exchanger 1 (AE1) and the sodium pump become immobilized at specialized microdomains of the lateral cell surface. Evidence is provided that both membrane proteins are linked via ankyrin to the spectrin-based membrane cytoskeleton that underlies the basolateral membrane domain. Linkage of these and other integral membrane proteins to the cytoskeleton may not only place them to specialized sites of the plasma membrane but may also prevent these transporters from clustering and endocytosis, thus helping them to stay at the cell surface. In search of sequence motifs involved in binding of integral membrane proteins to components of the cytoskeleton we found that the binding interface of AE1 to protein 4.1 (an actin and spectrin cross-linking protein) consists of a cluster of five amino acid residues, namely IRRRY in AE1 and LEEDY on protein 4.1. This motif may play a more general role in cytoskeleton membrane linkages.

ISSN:1420-4096    

DOI:10.1159/000173747

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In each nephron, a change in Cl delivered to the macula densa affects afferent arteriolar tone, and thus SNGFR. This phenomenon, called tubuloglomerular feedback (TGF), is the main function of the juxtaglomerular apparatus (JGA) and serves as the fine regulator of SNGFR. The phylogeny of the JGA strongly suggests that its physiological significance may be closely related to autoregulation of RPF and GFR and that JGA and TGF will allow maintenance of SNGFR in the face of low sodium intake. We propose that JGA, which appeared from amphibia, was a prerequisite, during evolution, for transition to terrestrial life style where abundant sodium intake was not guaranteed. In other words, our nephron is in essence a salt-conserving machinery to maintain SNGFR. Further, resetting of TGF or maladaptation of TGF in the presence of abundant salt intake may underlie the pathogenesis of essential hypertension.

ISSN:1420-4096    

DOI:10.1159/000173748

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Properties of ion channels of the cortical collecting duct (CCD) and their relevance for the macroscopic conductances are discussed. Although the regulation of the Na+ conductance by various hormones is widely studied, the relevant Na+ channel appears to be extremely difficult to be detected in the intact preparation. Three different K+ channels with slope conductances of about 30,140 and 80 pS (excised, 145 mmol/l KCL and 145 mmol/l NaCl on both sides of the membrane) have been found in principal cells of the CCD so far. The first two channels are located in the luminal, the latter one in the basolateral membrane. The two luminal channels are highly sensitive to the cytosolic pH and are also inhibited by cytosolic ATP. The small luminal K+ channel, highly active on the cell, is most likely responsible for K+ secretion. The large luminal K+ channel is involved in the volume regulation. The basolateral K+ channel, again highly active on the cell, is probably responsible for the recirculation of K+ across this membrane. The physiological role of the observed Cl- channels is still unknown.

ISSN:1420-4096    

DOI:10.1159/000173749

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Apical sodium-dependent transport of inorganic phosphate (Pi) in the proximal tubule plays a crucial role in renal Pi reabsorption and consequently in the maintenance of Pi homeostasis. This transport system represents a main target for acute and long-term regulation such as by parathyroid hormone, by growth factors and dietary intake of phosphate. In this short review we briefly describe the currently established cellular mechanism of proximal tubular Pi reabsorption and its regulation via the apical Na/Pi cotransport system. In a second part we will outline recent progress made with respect to the molecular cloning of renal Na/Pi cotransport systems. Knowledge about the molecular identity of these transport systems will make it possible to resolve yet unanswered questions about the molecular mechanisms involved in the physiology of the regulation of renal Pi reabsorption.

ISSN:1420-4096    

DOI:10.1159/000173750

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

To survive, cells have to avoid excessive alterations of their volume. To this end, cells have developed a complex machinery of cell volume regulatory mechanisms comprising transport across the cell membrane and metabolism. Upon cell swelling, they loose electrolytes mainly via selective K+ channels and unselective ion channels and/or KCl symport, upon cell shrinkage they accumulate ions by Na+, K+,2Cl- cotransport and parallel operation of Na+/H+ exchange and Cl-/ HC03- exchange. In addition, cell shrinkage stimulates glycogenolysis, proteolysis and formation of organic osmolytes such as amino acids, methylamines and polyols. Cell swelling stimulates formation of glycogen and proteins and cellular release of organic osmolytes. Alterations of cell volume do play a crucial role in the regulation of cell function, as illustrated by four examples: 1. Epithelial transport may lead to cell swelling, which then triggers volume regulatory mechanisms modifying transcellular transport.2. Insulin swells hepatocytes by activation of Na+, K+,2Cl- cotransport and Na+/H+ exchange, glucagon shrinks those cells by activation of ion channels. The respective volume changes participate in the regulation of cellular protein and glycogen metabolism by these hormones.3. Growth factors and expression of ras oncogene activate Na+ , K+ ,2Cl- cotransport and Na+/H+ exchange leading to the respective cell swelling.4. Hepatocyte swelling triggers a hepatorenal reflex decreasing renal blood flow.

ISSN:1420-4096    

DOI:10.1159/000173751

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

After a detailed description of early cellular, membrane and intracellular events in rat renal medullary collecting duct cells when exposed to hypotonicity, a synopsis on organic osmolyte transport properties possible trigger mechanisms and the cellular location of transport pathways is given. From the data currently available on renal and nonrenal cells, it is concluded that hypotonicity-evoked efflux of all organic osmolytes appears to be mediated by transport proteins which share a variety of properties more typical for channels than for carriers. A large diversity seems to exist, however, for the signalling mechanisms. Such diversity allows the cells to regulate the intracellular concentration of different organic osmolytes independently of each other, giving flexibility to the spectrum of osmotic responses. The site of release also varies from cell to cell; here conservation of organic osmolytes for future reuptake or further metabolism appears to be the major determinant.

ISSN:1420-4096    

DOI:10.1159/000173752

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have used in vitro techniques to study the metabolism of dexamethasone. Tissue slices, homogenates and microsomal fractions of various mammalian organs from rats and humans have been used. We focused particularly on the question of whether or not dexamethasone (Dexa) is oxidized at the C11-OH group by 11β-hydroxysteroid-dehydrogenase. High activities of this enzyme system for Dexa were localized in renal cortex and rectum. Material from both human and murine liver was ineffective. The main metabolite formed from Dexa in renal and intestinal systems was identified by different mass-spectrometric techniques including on line HPLC mass spectrometry as 11-dehydro-dexamethasone. This finding was corroborated by the observation that both corticosterone and glycyrrhetinic acid block the metabolic transformation of Dexa

ISSN:1420-4096    

DOI:10.1159/000173753

出版商:S. Karger AG    

年代:1993

数据来源: Karger