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)

Many hormones and drugs exert their effects on cells by increasing cytosolic Ca2+ (Cai2+) and activating protein kinase C (PKC). Each of these actions results in cholestasis in the isolated perfused rat liver, but the responsible mechanisms are unclear. We used isolated rat hepatocyte couplets to observe the direct effects of increased Cai2+ and PKC activation on permeability of the hepatocyte tight junction and canalicular volume, two possible determinants of hepatocyte bile secretion. Couplets were stimulated with the Ca2+ agonist vasopressin (10(-8) M) in the absence and presence of the Ca2+ influx antagonist Ni2+ (5 x 10(-3) M) or with the PKC activator phorbol dibutyrate (10(-6) M). Cai2+ was determined by ratio microspectrofluorometry of indo-1, permeability of the couplet tight junctions was assessed by exclusion of horseradish peroxidase from the canalicular space, and changes in canalicular volume over time were measured directly by optical planimetry. Canalicular volume increased by 1.6 +/- 2.5%/min (mean +/- SD) under basal conditions. In response to vasopressin, there was a rapid 15-fold increase in Cai2+, followed first by an increase in paracellular permeability, then by canalicular collapse (15.9 +/- 5.9%/min). Pretreatment with Ni2+ markedly decreased the vasopressin-induced increase in Cai2+ and abolished both the increase in paracellular permeability and the canalicular collapse. Phorbol dibutyrate also increased paracellular permeability but resulted in neither increased Cai2+ nor canalicular collapse. The PKC inhibitor H-7 reversed the effects of both vasopressin and phorbol dibutyrate on tight junction permeability. Bile secretory pressure, measured in isolated perfused rat liver preparations, was acutely increased by vasopressin, but the increase was augmented rather than inhibited by Ni2+.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets. 161 38

The mechanism for the vasopressin- and epinephrine-induced decrease in bile formation and increase in sinusoidal efflux of glutathione was investigated in rat livers perfused with recirculating fluorocarbon emulsion. Vasopressin and epinephrine transiently decreased bile flow and excretion of endogenous bile acids and glutathione and increased the bile/perfusate ratio of [14C]sucrose, suggesting an increase in junctional permeability, but had no effect on the bile/perfusate ratio of [3H]polyethylene glycol-900. The decreased biliary glutathione was balanced by an increase in sinusoidal efflux, such that total hepatic release remained unchanged. The adrenergic antagonist dihydroergotamine blocked the effects of epinephrine. To examine whether an increase in junctional permeability per se could account for the changes in glutathione efflux, biliary permeability was increased by either bile duct ligation, lowering of perfusate Ca2+ concentration with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), or addition of taurolithocholate, a cholestatic bile acid. All three maneuvers produced a decrease in biliary glutathione excretion and a concomitant increase in sinusoidal glutathione efflux, whereas total glutathione release was largely unaffected. The effects of EGTA were partially reversed if CaCl2 was reintroduced into the perfusate. Because the GSH/GSSG ratio in perfusate could not be measured in this experimental system due to the spontaneous oxidation of GSH to GSSG, additional experiments in the nonrecirculating mode examined the effects of vasopressin and bile duct ligation on sinusoidal release of GSH and GSSG. In control livers there was no detectable GSSG in perfusate (less than 0.5 nmol.min-1.g-1). After vasopressin administration, the additional sinusoidal glutathione was mainly as GSH, although there was also a significant amount of GSSG (1-2 nmol.min-1.g-1). The additional glutathione released into perfusate after bile duct ligation was 47% as GSSG. When vasopressin was administered to livers whose bile duct had been ligated, its ability to enhance sinusoidal glutathione release was diminished, suggesting that the effects of vasopressin and bile duct ligation are not additive. These observations support previous findings that vasopressin and epinephrine can modulate hepatocyte tight junctional permeability and demonstrate that these hormones produce cholestasis and inverse changes in sinusoidal and biliary glutathione efflux. Other maneuvers that increased biliary permeability to [14C]sucrose also produced cholestasis and a redistribution of glutathione efflux from bile to perfusate, suggesting that an increase in junctional permeability may allow biliary glutathione to reflux from bile to plasma.
 ...
PMID:Cholestasis, altered junctional permeability, and inverse changes in sinusoidal and biliary glutathione release by vasopressin and epinephrine. 211 13

The hypothesis that monohydroxy bile acids exert their cholestatic and hepatotoxic effects via a sustained elevation of cytosolic [Ca2+] was tested in the isolated perfused rat liver. Infusion of the specific inhibitor of microsomal Ca2+ sequestration, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) (25 microM for 10 min) produced efflux of Ca2+ from the liver and a sustained (20 min) increase in cytosolic [Ca2+] as indicated by the threefold increase in hepatic glucose output. Release of the endoplasmic reticular Ca2+ pool was demonstrated by the complete abolition of vasopressin- and phenylephrine-induced Ca2+ exchange between the liver and perfusate. Despite the profound perturbation of intracellular Ca2+ homeostasis produced by tBuBHQ, there was no decrease in bile flow and no evidence of hepatocellular injury (for 60 min), as indicated by lactate dehydrogenase release. In contrast, lithocholic acid (25 microM for 10 or 30 min) or taurolithocholic acid (5 microM for 10 or 30 min) produced an 80-90% inhibition of bile flow and a progressive increase in perfusate lactate dehydrogenase activity. During and after bile acid infusion, there was no change in Ca2+ fluxes between liver and perfusate, no stimulation of glucose output from the liver, and hormone-stimulated Ca2+ responses were preserved. It is concluded that the mechanisms for bile acid-induced cholestasis and hepatotoxicity in the intact liver are not attributable to changes in intracellular Ca2+ homeostasis, and especially not to prolonged release or depletion of Ca2+ sequestered in the endoplasmic reticulum.
 ...
PMID:Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver. 231 79

Gallbladder and extrahepatic bile duct operations merit special consideration in cirrhotic patients. During the past 15 years at Strong Memorial Hospital, 33 cirrhotic patients have undergone cholecystectomy or an operation for bile duct obstruction. Of the 21 patients with cirrhosis subjected to cholecystectomy for cholecystitis and cholelithiasis, nine had uncomplicated courses. Included in this group was one patient in whom the intrahepatic portion of the gallbladder was deliberately not resected. The other 12 patients (57%) had excessive intraoperative bleeding and required transfusion of three or more units of blood. One patient required additional exploratory surgery and antifibrinolytic therapy to control bleeding. In an additional group, only one of seven patients whose gallbladder was removed during a portal decompressive procedure bled excessively from the liver bed. A third group of five patients, including four with secondary biliary cirrhosis who underwent operations on the bile duct for obstruction, had massive intraoperative bleeding (greater than 5 U). Four of the five exsanguinated, and the remaining patient died of sepsis. A more conservative approach toward elective cholecystectomy in the cirrhotic patient is indicated. If an operation is performed, increased bleeding should be anticipated; extensive intrahepatic dissection should be avoided. Intraoperative infusion of vasopressin and an antifibrinolytic agent should be considered.
 ...
PMID:Biliary tract surgery and cirrhosis: a critical combination. 728 Sep 97

The actions of vasopressin and glucagon, administered alone or together, were assessed on bile flow in perfused livers from rats made cholestatic by the injection of ethynylestradiol and from those allowed to recover from such treatment. Concomitant measurements were made of biliary calcium output as well as changes in the perfusate Ca2+ concentration, glucose output, and oxygen uptake. Experiments were also conducted where cholestasis was induced in vitro in the perfused liver by the infusion of phalloidin. In each case cholestasis was demonstrated to have occurred by a reduction in bile flow by approximately 50%. The data show that the transient increase in bile flow and bile calcium seen in control rat liver soon after the administration of vasopressin, particularly when coadministered with glucagon, is largely absent in cholestasis induced by ethynylestradiol and attenuated in cholestasis induced by phalloidin. At the same time the pattern of perfusate Ca2+ fluxes in ethynylestradiol-induced cholestasis shifts to one reflecting net efflux of the ion from the liver. The responses to glucagon administration alone contrast with those of vasopressin in that in the perfused liver of ethynylestradiol-treated rats, glucagon induces a pronounced and sustained increase in bile flow. In cholestasis induced by both ethynylestradiol and phalloidin, glucagon fails to induce an initial transient decrease in bile flow. The effects of glucagon, including enhancement of vasopressin-stimulated bile flow in control and in ethynylestradiol-treated rats, can be mimicked by dibutyryl cyclic adenosine monophosphate (cAMP). Changes in glucose output and oxygen uptake induced by both hormones are only slightly attenuated. The data show that the modulation of bile flow that occurs rapidly after the administration of vasopressin and glucagon to control perfused rat liver is altered in conditions of cholestasis induced by either ethynylestradiol or phalloidin.
 ...
PMID:Hormone-induced bile flow and hepatobiliary calcium fluxes are attenuated in the perfused liver of rats made cholestatic with ethynylestradiol in vivo and with phalloidin in vitro. 773 53

Hepatic fatty change is a common lesion. Two forms are recognized: micro- and macrovesicular steatosis, the former being much less frequent and more serious than the latter. The case of an alcoholic woman under anticonvulsivant therapy and with medications for a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) who presented with rapidly progressive cholestasis and hepatocellular failure is reported. Massive macro- and micro-vesicular hepatic steatosis was diagnosed at autopsy. The authors review the clinico-pathological features associated with this condition, and causal factors possibly implicated in this case are discussed in regard with currently considered pathophysiological mechanisms.
 ...
PMID:Fatal massive liver steatosis--a clinicopathological case report. 926 Mar 33

Gap junctions are thought to be necessary for proper tissue function. However, no clear hepatic phenotype has been described in patients lacking connexin 32 (Cx32), the principal gap junction in liver. To determine the physiological role of Cx32 in liver, we compared the response of wild type and Cx32-deficient mice to endotoxin, since this stress increases serum levels of hormones that bind to receptors that are asymmetrically distributed across the hepatic lobule. In hepatocyte couplets isolated from wild type mice, most hepatocytes could transfer microinjected dye to their neighbor even after treatment with endotoxin. Dye transfer was not observed in Cx32-deficient couplets. Treatment of hepatocyte couplets from wild type mice with vasopressin induced calcium (Ca(2+)) waves that crossed the couplets in a concentration-dependent fashion, but the delay in transmission was markedly prolonged at all concentrations in Cx32-deficient couplets. Expression of the vasopressin receptor and the inositol 1,4,5-trisphosphate receptor was not decreased by endotoxin or in Cx32-deficient couplets. Finally, endotoxin caused transient hypoglycemia and cholestasis in wild type animals, but hypoglycemia was slightly prolonged and cholestasis was much worse in Cx32-deficient mice treated with endotoxin. The hepatic response to endotoxin is markedly impaired in the absence of Cx32. Thus, an important role of gap junctions in the liver is to assure integrated and uniform tissue response in times of stress.
 ...
PMID:Endotoxin unmasks the role of gap junctions in the liver. 1533 23

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is an extremely rare complication of infectious diseases. A rare case of brucellosis complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) cholestasis and pericardial involvement is reported. A 27-year-old woman was admitted for fever, abdominal pain, and scleral icterus. Her medical history revealed no recent use of diuretic agents. In addition to cholestasis and elevated liver enzymes, euvolemic hyponatremia, hypouricemia, low plasma osmolality, and high urinary osmolality were also detected. Surrenal and thyroid tests were also within normal range. Echocardiography revealed minimal pericardial effusion with normal cardiac functions. The final diagnosis was SIADH due to Brucellosis. Hyponatremia, cholestasis, and pericardial disease were resolved with effective antibrucellar treatment with streptomycine and doxycycline. After completing treatment of brucellosis, there was not any more evidence of cholestasis and pericardial fluid.
 ...
PMID:Syndrome of inappropriate secretion of antidiuretic hormone cholestasis and pericardial effusion due to brucellosis infection: a case report. 2082 43

The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.
 ...
PMID:Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease. 2757 Dec 15

A 44-year-old man with uncontrolled diabetes and chronic pancreatitis presented with abdominal pain, jaundice and unintentional weight loss. Laboratory investigations were significant for hyponatraemia, an obstructive pattern of liver enzymes. Imaging was consistent with intrahepatic and extrahepatic biliary obstruction, and endoscopic evaluation revealed a long common bile duct stricture. Intravascular volume depletion, beer potomania and syndrome of inappropriate antidiuretic hormone (with concern for biliary or pancreatic malignancy) were considered in the work-up for the aetiology of the hyponatraemia. After 4 days of conventional treatment, hyponatraemia persisted. Lipid panel obtained revealed very high levels of total cholesterol. The patient underwent a successful biliary diversion and reconstruction surgery. Follow-up after 3 months showed a clinically stable patient with resolution of elevated liver enzymes, hyperlipidaemia and hyponatraemia. We illustrate this rare case of hyponatraemia secondary to hyperlipidaemia in obstructive biliary cholestasis. It is important for physicians to thoroughly investigate the aetiology of hyponatraemia at its onset.
 ...
PMID:Pseudohyponatraemia secondary to hyperlipidaemia in obstructive jaundice. 2919 8


1