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

We investigated whether the motor protein cytoplasmic dynein and dynactin, a protein complex thought to link dynein with vesicles, are present in rat renal collecting ducts and associated with aquaporin-2 (AQP2)-bearing vesicles. Immunoblotting demonstrated cytoplasmic dynein heavy and intermediate chains in kidney, with relative expression levels of inner medulla > outer medulla > cortex. In addition to being present in cytoplasmic fractions, dynein was abundant in membrane fractions enriched for intracellular vesicles. Dynactin was also abundant in membrane fractions enriched for intracellular vesicles. Furthermore, both dynactin and dynein were present in vesicles specifically immunoisolated using anti-AQP2 antibodies. Immunocytochemistry revealed labeling for dynein in the collecting duct principal cells with a pattern consistent with labeling of intracellular vesicles. Moreover, quantitative double immunogold labeling confirmed colocalization of AQP2 and dynein in the same vesicles at the electron microscopic level. Thus the microtubule-associated motor protein dynein and the associated dynactin complex are present in rat renal collecting duct principal cells and are associated with intracellular vesicles, including those bearing AQP2, consistent with the view that dynein and dynactin are involved in vasopressin-regulated trafficking of AQP2-bearing vesicles.
 ...
PMID:Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct. 948 34

Cold preservation of kidneys is commonly used in human transplantation and in vitro studies. However, although disruption of the cytoskeleton by cold has been demonstrated in cultured cells, the effect of cold treatment on intact kidney is poorly understood. In this study, specific antibodies were used to examine the effect of hypothermia on the cytoskeletal network and the trafficking of some membrane proteins in the urinary tubule. Rat kidneys were cut into thin slices (approximately 0.5 mm) that were divided into several groups: (1) some were immediately fixed in paraformaldehyde, sodium periodate, and lysine (PLP); (2) some were stored at 4 degrees C for 15 min or 4 h before being fixed in cold PLP; or (3) after 4 h cold treatment, some slices were rewarmed to 37 degrees C for 15, 30, and 60 min in a physiologic solution, pH 7.4, and were then fixed in warm PLP. Immunofluorescence staining revealed an almost complete disruption of the microtubule network in proximal tubules after 15 min cold treatment, whereas microtubules in other segments were affected after 4 h. A partial recovery of the microtubule network was observed after 60 min rewarming. In contrast, actin filaments seemed to be resistant to cold treatment. gp330, aquaporin-2, H+ ATPase, and the AE1 anion exchanger were all relocated into numerous vesicles that were distributed throughout the cytoplasm after hypothermia followed by rewarming, whereas Na-K-ATPase retained its basolateral localization. The vasopressin-stimulated insertion of aquaporin-2 water channels into the apical membrane was inhibited during the initial rewarming period after cold exposure. Thus, cold preservation of tissues might impair, at least transiently, the polarized membrane expression and function of some transport proteins in renal epithelial cells.
 ...
PMID:Cold-induced microtubule disruption and relocalization of membrane proteins in kidney epithelial cells. 952 91

Since the molecular identification of the first aquaporin in 1992, the number of proteins known to belong to this family has been rapidly increasing. These members may be separated into two subgroups based on gene structure, sequence homology, and function. Regulation of the water permeability of the collecting ducts of the kidney is essential for urinary concentration. Aquaporin-2 and -3, which are representative of these subgroups, are colocalized in the collecting ducts. Understanding these subgroups will elucidate the differences between aquaporin-2 and -3. Aquaporin-2 is a vasopressin-regulated water channel located in the apical membrane, and aquaporin-3 is a constitutive water channel located in the basolateral membrane. In contrast to aquaporin-3, which appears to be less well regulated, many studies have now identified multiple regulational mechanisms at the gene, protein, and cell levels for aquaporin-2, thus reflecting its physiological importance. Evidence of the participation of aquaporin-2 in the pathophysiology of water-balance disorders is accumulating.
 ...
PMID:Aquaporin-2 and -3: representatives of two subgroups of the aquaporin family colocalized in the kidney collecting duct. 955 61

Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct water channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary expression of the descending limb water channel, aquaporin-1, was not significantly altered, pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity.
 ...
PMID:Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome. 957 61

The expressions of aquaporin-1 (AQP-1) in cultured mIMCD-3 cells were studied. There was no detectable AQP-1 in cells grown in serum-containing growth medium (SM, 297 +/- 2 mOsm/kg. H2O). When SM was supplemented with NaCl (406 +/- 2 mOsm/kg. H2O), cellular AQP-1 was induced. A further increase in medium osmolarity with NaCl (493 +/- 3 mOsm/kg. H2O) had conferred cells an 2.5 to 3-fold increase of AQP-1 expression over those grown in the 406 +/- 2 mOsm/kg. H2O medium. Moreover, AQP-1 was found to be translocated from cytosol to membrane. In addition, exposing the mIMCD-3 cells to vasopressin (AVP, 10(-8) M) and/or NaCl-supplemented serum-free media (496 +/- 3 mOsm/kg. H2O) for 6h did not render them to produce AQP-1. However, AQP-1 was induced after 24h of incubation, with an 1.5-fold additive effect by AVP. Our RT-PCR data had confirmed the NaCl inducibility and AVP synergism in AQP-1 expression at both mRNA and protein levels. This suggests a new role for cellular AQP-1 and AVP in overcoming osmotic stress in an in vitro system.
 ...
PMID:Aquaporin-1: an osmoinducible water channel in cultured mIMCD-3 cells. 958 95

Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.
 ...
PMID:Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum. 968 19

The acute effect of treatment with the vasopressin V2-receptor antagonist OPC-31260 (OPC) on aquaporin-2 (AQP2) distribution and expression in rat kidney was examined. Immunofluorescence and semi-quantitative immunoelectron microscopy revealed that 15 and 30 min of OPC treatment resulted in significant reduction in apical plasma membrane labeling of AQP2, with a concomitant increase in labeling of vesicles and multivesicular bodies. In parallel, OPC treatment induced a large increase in urine output [0.6 +/- 0.2 vs. 8.3 +/- 1.0 ml/h (n = 4)]. Northern blotting using a 32P-labeled AQP2 cDNA probe and a digoxigenin-labeled AQP2 RNA probe revealed a band of approximately 1.6 kb corresponding to the predicted size of AQP2 mRNA. In control experiments, thirsting increased, whereas water loading decreased AQP2 mRNA levels. Treatment of rats with OPC caused a significant reduction in AQP2 mRNA within 30 min (52 +/- 21%, n = 8, P < 0.025) and 60 min (56 +/- 7%, n = 4, P < 0.001) of treatment compared with intravenous saline-injected controls. Thus a very rapid reduction in AQP2 mRNA was observed in response to vasopressin-receptor antagonist treatment. The reduction in AQP2 mRNA persisted after 24 h (40 +/- 17%, n = 5, P < 0.05) of OPC treatment. There was a parallel increase in diuresis and reduction in urine osmolality. In conclusion, V2-receptor blockade produced a rapid internalization of AQP2 parallel with a rapid increase in urine output. Furthermore, OPC treatment caused a rapid and significant reduction in AQP2 mRNA expression, demonstrating that for rapid regulation of AQP2 expression, modulation of AQP2 mRNA levels is regulated via vasopressin-receptor signaling pathways.
 ...
PMID:Acute effects of vasopressin V2-receptor antagonist on kidney AQP2 expression and subcellular distribution. 969 Oct 20

Glycosylation has been shown to be important for proper routing and membrane insertion of a number of proteins. In the collecting duct, aquaporin-2 (AQP2) is inserted into the apical membrane after stimulation of vasopressin type-2 receptors and retrieved into an endosomal compartment after withdrawal of vasopressin. The extent of glycosylation of AQP2 in human kidney and urine and the effects of deglycoylation on routing of AQP2 in an AQP2-transfected Madin-Darby canine kidney cell line (clone WT10) were investigated. Semiquantitative immunoblotting of human kidney membranes and urine showed an AQP2 glycosylation of 35 to 45% for medulla, papilla, and urine, with low variation among individuals. The 1-desamino-8-D-arginine vasopressin-induced transcellular osmotic water permeability (Pf) of WT10 cells by a factor of 2.6 +/- 0.2 was reduced to 1.5 +/- 0.1 after pretreatment with the glycosylation inhibitor tunicamycin. However, when WT10 cells were incubated with 8-br-cAMP, the Pf increased by a factor 2.8 +/- 0.2 and by 2.9 +/- 0.2 after prior incubation with tunicamycin. Immunoblot analyses revealed that in WT10 cells, 34% of AQP2 is glycosylated, which was reduced to 2% after tunicamycin treatment. Surface biotinylation and subsequent semiquantitative immunoblotting revealed that stimulation by cAMP increased the level of AQP2 in the apical membrane of WT10 cells 1.5-fold. independent of the presence of tunicamycin. However, in tunicamycin-treated WT10 cells, all AQP2 in the apical membrane was unglycosylated, whereas in untreated cells 30% of AQP2 in the apical membrane was glycosylated. These results prove that glycosylation has no function in the routing of AQP2 in Madin-Darby canine kidney cells.
 ...
PMID:Glycosylation is not essential for vasopressin-dependent routing of aquaporin-2 in transfected Madin-Darby canine kidney cells. 972 61

Urinary concentrating capacity is regulated in part by a long-term adaptational process involving changes in the absolute abundance of the aquaporin-2 water channel in collecting duct cells. Alterations in aquaporin-2 abundance play key roles in the pathophysiology of several water balance disorders. Escape from the antidiuretic action of vasopressin, e.g. in the syndrome of inappropriate antidiuretic hormone secretion, involves a selective downregulation of aquaporin-2 expression. Excessive water retention causing hyponatremia in volume-expanded states such as congestive heart failure appears to be due in part to a failure of this escape mechanism.
 ...
PMID:Long-term regulation of urinary concentrating capacity. 972 4

To examine the involvement of vasopressin and dehydration in the regulation of aquaporin-2 (AQP2) expression in rat kidney, we investigated the effects of treatment for 60 h with the specific V2-receptor antagonist OPC-31260 (OPC), alone and in conjunction with dehydration for the last 12 h. Changes in AQP2 protein and mRNA expression in kidney inner medulla were determined by Western and Northern blotting, and AQP2 distribution was analyzed by immunocytochemistry and immunoelectron microscopy. Treatment with OPC increased urine output fourfold, with a reciprocal decrease in urine osmolality. AQP2 expression decreased to 52 +/- 11% of control levels (n = 12, P < 0.05), and AQP2 was found predominantly in intracellular vesicles in collecting duct principal cells. This is consistent with efficient blockade of the vasopressin-induced AQP2 delivery to the plasma membrane and with the observed increased diuresis. Consistent with this, AQP2 mRNA levels were also reduced in response to prolonged OPC treatment (30 +/- 10% of control levels, n = 9). Five days of treatment with furosemide, despite producing even greater polyuria than OPC, was not associated with downregulation of AQP2 levels, demonstrating that AQP2 downregulation is not secondary to increased urine flow rate or loss of medullary hypertonicity. During 12-h thirsting in the continued presence of OPC, urine output dropped dramatically, to levels not significantly different from that seen in (nonthirsted) control animals. In parallel with this, AQP2 levels rose to control levels. Control experiments confirmed continued effective receptor blockade. These results indicate that the V2-receptor antagonist causes a modest decrease in AQP2 expression that is not a consequence of increased urine flow rate or washout of medullary hypertonicity. However, this decrease is much less marked than that seen in some forms of acquired nephrogenic diabetes insipidus. In conjunction with the effects of thirsting, this suggests that modulation of AQP2 expression is mediated partly, but not exclusively, via V2 receptors.
 ...
PMID:Dehydration reverses vasopressin antagonist-induced diuresis and aquaporin-2 downregulation in rats. 972 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>