Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the amphibian urinary bladder, the increase in water permeability induced by antidiuretic hormone (ADH) is accompanied by the appearance of apical intramembrane particle (IMP) aggregates that are believed to contain specific channels for water. In a previous work, we have shown that 3,3'-diallyldiethylstilbestrol (DADES), a synthetic estrogen which is a blocker of the glucose transporter, also inhibits the hydrosmotic response to ADH in the bladder. Our aim in the present study was to analyze the alterations of the membrane fine structure further and to correlate them with the water permeability changes. The results point to a selective inhibition of the ADH-induced net water flow, probably due to an interference with one of the last steps of the response to the hormone. This inhibition is associated with an increase in the density of the apical IMP aggregates, which are thus probably not operational. The resting net water flow is not inhibited and, surprisingly, typical IMP aggregates are frequently observed in the apical membrane after DADES treatment. The compound also induces the appearance of unusual loose IMP clusters that can only be seen on the apical membrane of the granular cells and that share several ultrastructural similarities with the ADH-induced aggregates. These results suggest that 1) apical DADES treatment stimulates the insertion of IMP aggregates in the apical membrane of the urinary bladder and 2) DADES inhibits the ADH-induced water flow by interfering with the aggregates and thus probably by blocking the specific water channels.
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PMID:ADH-induced water permeability and particle aggregates: alteration by a synthetic estrogen. 185 96

The cellular uptake of a model antisense oligonucleotide complementary to 21 bases of the bovine GLUT-1 glucose transporter mRNA and a model vasopressin peptide that were biotinylated, was markedly stimulated by the presence of avidin, a cationic protein. Conversely, the bacteria homologue of avidin, streptavidin, which is a slightly acidic protein, did not facilitate cellular uptake. The avidin-mediated uptake of biotinylated derivatives was competitively inhibited by another cationic protein, protamine, with a Ki of 5 micrograms/ml; was saturable, temperature- and time-dependent; and was associated with endocytosis. The use of the avidin-biotin system provides a new approach to increasing the cellular uptake of antisense oligonucleotides or peptides.
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PMID:Enhanced cellular uptake of biotinylated antisense oligonucleotide or peptide mediated by avidin, a cationic protein. 187 60

Cells can rapidly and reversibly alter solute transport rates by changing the kinetics of transport proteins resident within the plasma membrane. Most notably, this can be brought about by reversible phosphorylation of the transporter. An additional mechanism for acute regulation of plasma membrane transport rates is by the regulated exocytic insertion of transport proteins from intracellular vesicles into the plasma membrane and their subsequent regulated endocytic retrieval. Over the past few years, the number of transporters undergoing this regulated trafficking has increased dramatically, such that what was once an interesting translocation of a few transporters has now become a widespread modality for regulating plasma membrane solute permeabilities. The aim of this article is to review the models proposed for the regulated trafficking of transport proteins and what lines of evidence should be obtained to document regulated exocytic insertion and endocytic retrieval of transport proteins. We highlight four transporters, the insulin-responsive glucose transporter, the antidiuretic hormone-responsive water channel, the urinary bladder H(+)-ATPase, and the cystic fibrosis transmembrane conductance regulator Cl- channel, and discuss the various approaches taken to document their regulated trafficking. Finally, we discuss areas of uncertainty that remain to be investigated concerning the molecular mechanisms involved in regulating the trafficking of proteins.
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PMID:Role of membrane trafficking in plasma membrane solute transport. 751 93

Progressive dehydration due to water deprivation and streptozotocin diabetes both produce increased activity of the hypothalamoneurohypophysial system and enhanced vasopressin secretion. To determine whether enhanced metabolic activity affects glucose transporter protein expression, this study examined the effect of these conditions on 45-kDa GLUT-1 and the neuronal glucose transporter, GLUT-3, which mediate glucose transport in the rat neurohypophysis. Progressive water deprivation increased hematocrit, plasma electrolytes Na+ and Cl-, and vasopressin over 3 days, relative to the severity of dehydration. Plasma vasopressin increased threefold by 24 h, reaching 4.5-fold by 72 h. These changes were reflected in a 56 and 75% decrease in neurohypophysial vasopressin content by 48 and 72 h, respectively. Significant changes in glucose transporters were also observed at 48 and 72 h, with GLUT-1 increasing by 18 and 44% and GLUT-3 increasing by 42 and 55%, respectively. Streptozotocin-induced diabetes produced increases in hematocrit, plasma Cl-, and vasopressin, although the magnitude of these changes was less than with dehydration. There was a twofold increase in plasma vasopressin by 3 days, commensurate with the onset of overt diabetes, and a threefold increase by 2 wk. These changes were reflected in a 30 and 40% decline in neural lobe vasopressin content, respectively. Despite the difference in the magnitude of hormone response, GLUT-3 increased by the same amount (53%) as in dehydration. GLUT-1, however, was decreased 16% by 3 days and 25% by 1 and 2 wk of diabetes. Although the opposite effects on GLUT-1 may relate to differences in circulating insulin or glucose, this study is the first demonstration of increased expression of GLUT-3 in response to a common hypothalamic signal in these two conditions.
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PMID:Altered expression of GLUT-1 and GLUT-3 glucose transporters in neurohypophysis of water-deprived or diabetic rats. 794 11

In previous studies we have shown that the insulin-responding glucose transporter isoform of 3T3-L1 adipocytes, GluT4, is almost completely located on microvilli. Furthermore, insulin caused the integration of these microvilli into the plasma membrane, suggesting that insulin-induced stimulation of glucose uptake may be due to the destruction of the cytoskeletal diffusion barrier formed by the actin filament bundle of the microvillar shaft regions [Lange et al. (1990) FEBS Lett. 261, 459-463; Lange et al. (1990) FEBS Lett. 276, 39-41]. Similar shape changes in microvilli were observed when the transport rates of adipocytes were modulated by glucose feeding or starvation. Here we demonstrate that the action of insulin on the surface morphology of hepatocytes is identical to that on 3T3L1 adipocytes; small and narrow microvilli on the surface of unstimulated hepatocytes were rapidly shortened and dilated on top of large domed surface areas. The aspect and mechanism of this effect are closely related to "membrane ruffling" induced by insulin and other growth factors. Pretreatment of hepatocytes with the PI 3-kinase inhibitor wortmannin (100 nM), which completely prevents transport stimulation by insulin in adipocytes and other cell types, also inhibited insulin-induced shape changes in microvilli on the hepatocyte surface. In contrast, vasopressin-induced microvillar shape changes in hepatocytes [Lange et al. (1997) Exp. Cell Res. 234, 486-497] were insensitive to wortmannin pretreatment. These findings indicate that PI 3-kinase products are necessary for stimulation of submembrane microfilament dynamics and that cytoskeletal reorganization is critically involved in insulin stimulation of transport processes. The mechanism of the insulin-induced cytoskeletal reorganization can be explained on the basis of the recent finding of Lu et al. [Biochemistry 35(1996) 14027-14034] that PI 3-kinase products exhibit much higher affinity for the profilin-actin complex than the primary products, PIP and PIP2. Thus, activated PI 3-kinase may direct a flux of profilin-actin complexes to the membrane locations of activated insulin receptors, where, due to the release of actin monomers after binding of profilactin to PI(3,4)P2 and PI(3,4,5)P3, massive actin polymerization is initiated. As a consequence, PI 3-kinase activation initiates a vectorial reorganization of the cellular actin system to membrane sites neighboring activated insulin receptors, giving rise to local membrane stress as visualized by extensive surface deformations and shortening of microvilli. In addition, extensive high-affinity binding of F-actin-barbed endcapping proteins enhances the cytoplasmic concentration of rapidly polymerizing filament ends. Consequently, the actin monomer concentration is lowered and the (cytoplasmic) pointed ends of the microvillar shaft bundle depolymerize and become shorter. The observations presented strengthen the previously postulated diffusion-barrier concept of glucose- and ion-uptake regulation and provide a mechanistic basis for explaining the action of insulin and other growth factors on transport processes across the plasma membrane.
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PMID:Action of insulin on the surface morphology of hepatocytes: role of phosphatidylinositol 3-kinase in insulin-induced shape change of microvilli. 951 32

In the magnocellular nuclei of the hypothalamus, there is a rich vascular network for which the function remains to be established. In the supraoptic nucleus, the high vascular density may be one element, which together with the water channel aquaporin-4 expressed in the astrocytes, is related to a role in osmoreception. We tested the osmoreception hypothesis by studying the correlation between vascular and cellular densities in the paraventricular nucleus and the supraoptic nucleus. Whether aquaporin-4 is likely to contribute to osmoreception was tested by studying the distribution in the magnocellular nuclei of the hypothalamus. The high vascular density may also reflect a high metabolic activity due to the synthesis of vasopressin and oxytocin. This metabolic hypothesis was tested by studying the regional cytochrome oxidase histochemistry, the local cerebral blood flow, and the density of glucose transporter type-1 in the supraoptic and paraventricular nuclei. All the magnocellular nuclei were characterized by an extended and intense aquaporin-4 labelling and a weak cytochrome oxidase histochemistry. The highest vascular density was found in the supraoptic nucleus and the magnocellular regions of the paraventricular nucleus. The local cerebral blood flow rates were surprisingly low in the paraventricular nucleus and the supraoptic nucleus in comparison to the cerebral cortex. Furthermore in these nuclei, the antibody for glucose transporter type-1 revealed two populations of vessels differing by their labelling intensity. The similarities observed between the different nuclei suggest that, in the hypothalamus, all magnocellular regions sense the plasma osmolarity. The low local cerebral blood flow, and the patterns of glucose transporter type-1 labelling and cytochrome oxidase histochemistry suggest that the high vascularization of these hypothalamic nuclei is not related to a high metabolic capacity in basal conditions.
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PMID:Hypervascularization in the magnocellular nuclei of the rat hypothalamus: relationship with the distribution of aquaporin-4 and markers of energy metabolism. 1101 36

GLUTX1 or GLUT8 is a newly characterized glucose transporter isoform that is expressed at high levels in the testis and brain and at lower levels in several other tissues. Its expression was mapped in the testis and brain by using specific antibodies. In the testis, immunoreactivity was expressed in differentiating spermatocytes of type 1 stage but undetectable in mature spermatozoa. In the brain, GLUTX1 distribution was selective and localized to a variety of structures, mainly archi- and paleocortex. It was found in hippocampal and dentate gyrus neurons as well as amygdala and primary olfactory cortex. In these neurons, its location was close to the plasma membrane of cell bodies and sometimes in proximal dendrites. High GLUTX1 levels were detected in the hypothalamus, supraoptic nucleus, median eminence, and the posterior pituitary. Neurons of these areas synthesize and secrete vasopressin and oxytocin. As shown by double immunofluorescence microscopy and immunogold labeling, GLUTX1 was expressed only in vasopressin neurons. By immunogold labeling of ultrathin cryosections microscopy, GLUTX1 was identified in dense core vesicles of synaptic nerve endings of the supraoptic nucleus and secretory granules of the vasopressin positive neurons. This localization suggests an involvement of GLUTX1 both in specific neuron function and endocrine mechanisms.
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PMID:Immunolocalization of GLUTX1 in the testis and to specific brain areas and vasopressin-containing neurons. 1175 19

Insulin-regulated aminopeptidase (IRAP) is a membrane aminopeptidase and is homologous to the placental leucine aminopeptidase, P-LAP. IRAP has a wide distribution but has been best characterized in adipocytes and myocytes. In these cells, IRAP colocalizes with the glucose transporter GLUT4 to intracellular vesicles and, like GLUT4, translocates from these vesicles to the cell surface in response to insulin. Earlier studies demonstrated that purified IRAP cleaves several peptide hormones and that, concomitant with the appearance of IRAP at the surface of insulin-stimulated adipocytes, aminopeptidase activity toward extracellular substrates increases. In the present study, to identify in vivo substrates for IRAP, we tested potential substrates for cleavage by IRAP-deficient (IRAP(-/-)) and control mice. We found that vasopressin and oxytocin were not processed from the NH(2) terminus by isolated IRAP(-/-) adipocytes and skeletal muscles. Vasopressin was not cleaved from the NH(2) terminus after injection into IRAP(-/-) mice and exhibited a threefold increased half-life in the circulation of IRAP(-/-) mice. Consistent with this finding, endogenous plasma vasopressin levels were elevated twofold in IRAP(-/-) mice, and vasopressin levels in IRAP(-/-) brains, where plasma vasopressin originates, showed a compensatory decrease. We further established that insulin increased the clearance of vasopressin from control but not from IRAP(-/-) mice. In conclusion, we have identified vasopressin as the first physiological substrate for IRAP. Changes in plasma and brain vasopressin levels in IRAP(-/-) mice suggest a significant role for IRAP in regulating vasopressin. We have also uncovered a novel IRAP-dependent insulin effect: to acutely modify vasopressin.
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PMID:Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP. 1768 3

TBC1D4 (or AS160) was identified as a Rab-GTPase activating protein (Rab-GAP) that controls insulin-dependent trafficking of the glucose transporter GLUT4 in skeletal muscle cells and in adipocytes. Recent in vitro cell culture studies suggest that TBC1D4 may also regulate the intracellular trafficking of kidney proteins such as the vasopressin-dependent water channel AQP2, the aldosterone-regulated epithelial sodium channel ENaC, and the Na(+)-K(+)-ATPase. To study the possible role of TBC1D4 in the kidney in vivo, we raised a rabbit polyclonal antibody against TBC1D4 to be used for immunoblotting and immunohistochemical studies. In immunoblots on mouse kidney homogenates, the antibody recognizes specific bands at the expected size of 160 kDa and at lower molecular weights, which are absent in kidneys of TBC1D4 deficient mice. Using a variety of nephron-segment-specific marker proteins, immunohistochemistry reveals TBC1D4 in the cytoplasm of the parietal epithelial cells of Bowman's capsule, the thin and thick limbs of Henle's loop, the distal convoluted tubule, the connecting tubule, and the collecting duct. In the latter, both principal as well as intercalated cells are TBC1D4-positive. Thus, with the exception of the proximal tubule, TBC1D4 is highly expressed along the nephron and the collecting duct, where it may interfere with the intracellular trafficking of many renal transport proteins including AQP2, ENaC and Na(+)-K(+)-ATPase. Hence, TBC1D4 may play an important role for the control of renal ion and water handling and hence for the control of extracellular fluid homeostasis.
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PMID:Immunofluorescent localization of the Rab-GAP protein TBC1D4 (AS160) in mouse kidney. 2246 39

Several studies have demonstrated a link between diabetes and the dysfunction of the inner ear. Few studies, however, have reported the signalling mechanisms involved in metabolic control in human inner ear cells. Knowledge of the expression and role of the insulin receptor and downstream signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. IRS1 and PDE1C are selectively expressed in sensory epithelial hair cells, whereas the other components are expressed in sensory epithelial supporting cells or in both cell types, as judged from co-expression or non-co-expression with glial fibrillary acidic protein, a marker for supporting cells. Furthermore, IRS1 appears to be localized in association with sensory nerves, whereas GLUT4 is expressed in the peri-nuclear area of stromal cells, as is the case for aquaporin 2. Thus, the insulin receptor, insulin signalling components and selected cAMP signalling components are expressed in the human saccule. In addition to well-known mechanisms of diabetes complications, such as neuropathy and vascular lesions, the expression of these proteins in the saccule could have a role in the observed link between diabetes and balance/hearing disorders.
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PMID:Expression of insulin signalling components in the sensory epithelium of the human saccule. 2358 6


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