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)

Water permeability of the basolateral membrane was estimated in isolated fragments of OMCD or IMCD in the Wistar rats. Apical surface of the fragments was blocked with oil injected into the lumen. Apparent water permeability coefficient (Pf) was measured by the rate of epithelium swelling following transition from hypertonic to isotonic medium (600 mOsm to 300 mOsm). Water deprivation caused significant increase in the Pf value in OMCD and IMCD fragments. Desmopressin (10(-8) M) increased water permeability in hydrated rats both in OMCD and IMCD. Mercury chloride decreased the Pf and abolished the effect of desmopressin in reversible manner. Estimation of aquaporins 2, 3, 4 mRNA content in the renal medulla was performed by semi-quantitative RT-PCR. Content of AQP4 and AQP2 mRNA in dehydrated animals was significantly higher than in hydrated ones both in outer medulla and inner medulla. Expression of AQP3 increased during dehydration only in the inner medulla. The findings reveal that water permeability of OMCD and IMCD can be increased by physiological stimuli, e.g. water deprivation. The activation of gene expression of the key elements of vasopressin signal system seems to contribute to this reaction.
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PMID:[Water permeability of the OMCD and IMCD cells' basolateral membrane under the conditions of dehydration and dDAVP action]. 1546 10

Desmopressin is a synthetic vasopressin analogue mainly used in treatment of diabetes insipidus and nocturia. Studies in rats have revealed a sex difference in the response to a vasopressin infusion, which was diminished after treatment with an NSAID. This study was performed in man to investigate the influence of sex and concomitant treatment of piroxicam on the pharmacokinetics and dynamics of desmopressin, and to validate a previously described indirect response model. Eight healthy males and eight healthy females participated in the trial, which was conducted in a pharmacokinetic (PK) part followed by a pharmacodynamic (PD) part. Desmopressin was administered intravenously as a single dose (PK = dose 2 microg, PD = dose 0.2 microg). Piroxicam was administered to achieve steady state. The pharmacokinetic parameters of desmopressin were estimated and calculated by means of two-compartmental analysis. In the dynamic part a study design based on an oral hydration model was used. Parameters for urine flow and urine osmolality were estimated. Individual estimates of the pharmacokinetic parameters served as input to the indirect response model that subsequently was fitted to urine osmolality data. The pharmacokinetics of desmopressin after a fixed bolus injection was neither influenced by piroxicam nor sex of the subject. The pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically significant when the effects were submaximal (>4.5 h after dose). The sex differences were diminished after pre-treatment with piroxicam, indicating a prostaglandin PGE(2)-mediated mechanism. The indirect response model was confirmed, although the modelling could not distinguish a sex difference, indicating a limitation of this model compared with traditional descriptive statistics.
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PMID:A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model. 1552 45

Desmopressin, a synthetic antidiuretic hormone analogue, is the only drug currently approved for the treatment of nocturia associated with nocturnal polyuria or multiple sclerosis (MS). Compared with vasopressin, desmopressin has a longer lasting and more potent antidiuretic effect and is devoid of vasopressor and uterotonic effects. In two large, randomised, double-blind phase III trials in adults with nocturia associated with nocturnal polyuria, 3 weeks of oral desmopressin therapy was significantly more effective than placebo in reducing the mean number of nocturnal voids and in normalising the rate of nocturnal urine production. Beneficial effects of desmopressin on nocturia were maintained and increased in patients completing 10 or 12 months of further treatment in a nonblind extension of short-term trials. In randomised, double-blind trials in MS patients with nocturia, nasal desmopressin reduced the mean number of nocturnal voiding episodes by 31-54%. In both patient populations, desmopressin increased the initial sleep period or mean maximum period of uninterrupted sleep by approximately 2 hours, an outcome significantly greater than that achieved with placebo. In trials of < or =6 weeks duration in adults with nocturia, desmopressin was generally well tolerated. Most desmopressin-related adverse events were transient and mild or moderate in severity. Clinically significant hyponatraemia was reported in approximately 5% and required withdrawal from studies in < or =3% of patients.
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PMID:Desmopressin: in adults with nocturia. 1561 55

Hemophilia A (HA) is a bleeding disorder caused by factor VIII (FVIII) deficiency. FVIII replacement therapy can reduce bleeding but is expensive, inconvenient, and complicated by development of antibodies that inhibit FVIII activity in 30% of patients. Neonatal hepatic gene therapy could result in continuous secretion of FVIII into blood and might reduce immunological responses. Newborn HA mice and dogs that were injected i.v. with a retroviral vector (RV) expressing canine B domain-deleted FVIII (cFVIII) achieved plasma cFVIII activity that was 139 +/- 22% and 116 +/- 5% of values found in normal dogs, respectively, which was stable for 1.5 yr. Coagulation tests were normalized, no bleeding had occurred, and no inhibitors were detected. This is a demonstration of long-term fully therapeutic gene therapy for HA in a large animal model. Desmopressin (DDAVP; 1-deamino-[d-Arg(8)]vasopressin) is a drug that increases FVIII activity by inducing release of FVIII complexed with von Willebrand factor from endothelial cells. It has been unclear, however, if the FVIII is synthesized by endothelial cells or is taken up from blood. Because the plasma cFVIII in these RV-treated dogs derives primarily from transduced hepatocytes, they provided a unique opportunity to study the biology of the DDAVP response. Here we show that DDAVP did not increase plasma cFVIII levels in the RV-treated dogs, although von Willebrand factor was increased appropriately. This result suggests that the increase in FVIII in normal dogs after DDAVP is due to release of FVIII synthesized by endothelial cells.
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PMID:Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy. 1583 21

In this paper we have reviewed the position of desmopressin in the treatment of diabetes insipidus. Desmopressin is a synthetic analog of vasopressin, with more pronounced antidiuretic effect. It is treatment of choice in substitution therapy of diabetes insipidus. Its application before sleeping time can reduce nocturnal enuresis, so it has a place in the treatment of enuresis nocturna. Antidiuretic effect of desmopressin is the result of agonistic effect on V2 receptors in the renal tubules. The efficacy and safety of desmopressin in mentioned indications was confirmed in clinical studies.
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PMID:Modern approach in treatment of diabetes insipidus. 1605 53

The vasopressin V2 receptor (V2R) belongs to the Class A G protein-coupled receptors (GPCRs). V2R is expressed in the renal collecting duct (CD), where it mediates the antidiuretic action of the neurohypophyseal hormone arginine vasopressin (CYFQNCPRG-NH2, AVP). Desmopressin ([1-deamino, 8-D]AVP, dDAVP) is strong selective V2R agonist with negligible pressor and uterotonic activity. In this paper, the interactions responsible for binding of dDAVP to vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors has been examined. Three-dimensional activated models of the receptors were constructed using the multiple sequence alignment and the complex of activated rhodopsin with Gt(alpha) C-terminal peptide of transducin MII-Gt(alpha) (338-350) prototype (Slusarz, R.; Ciarkowski, J. Acta Biochim Pol 2004 51, 129-136) as a template. The 1-ns unconstrained molecular dynamics (MD) of receptor-dDAVP complexes immersed in the fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) membrane model was conducted in an Amber 7.0 force field. Highly conserved transmembrane residues have been proposed as being responsible for V2R activation and G protein coupling. Molecular mechanism of the dDAVP binding has been suggested. The internal water molecules involved in an intricate network of the hydrogen bonds inside the receptor cavity have been identified and their role in the stabilization of the agonist-bound state proposed.
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PMID:Investigation of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors: molecular dynamics simulation of the agonist-bound state in the membrane-aqueous system. 1633 59

Chronic diabetes mellitus (DM) induces hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA). Our present study addresses the role of vasopressin (AVP) in maintaining adrenocortical responsiveness during DM. AVP-deficient mutant Brattleboro rats were used with heterozygous controls and the V2 agonist, desmopressin was infused to replace peripheral AVP. To induce DM the rats were injected by streptozotocin (STZ, 60 mg/ml/kg i.v.) and studied 2 weeks later. The acute stress stimulus was 60 min restraint. The signs of DM (the increase in water consumption and in blood glucose levels) were discovered in all rats. The diuretic effect of the lack of AVP was additional to the DM-induced osmotic diuresis. DM induced significant, chronic stress-like somatic changes on which AVP-deficiency had no effect and although desmopressin infusion normalized the water consumption and the body weight gain in AVP-deficient rats, it had no effect on DM-induced changes. The acute stress-induced plasma ACTH elevation was smaller in AVP-deficient or DM rats but these effects were not additive. Desmopressin did not normalize the decreased ACTH-elevation of AVP-deficient animals. The resting morning plasma corticosterone level was elevated both in DM and AVP-deficient rats without interaction. The restraint-induced corticosterone rise was influenced neither by the lack of AVP nor by DM and the basal and stress-induced prolactin levels were smaller in DM rats without any effect of AVP-deficiency. In conclusion, our data suggest that AVP does not play a crucial role in HPA axis regulation during DM-induced chronic stress. In contrast, the role of AVP seems to be more important during acute stress, however, it is restricted to the ACTH regulation. According to the water consumption data diabetes insipidus seems to be an additional risk factor for DM.
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PMID:The role of vasopressin in diabetes mellitus-induced hypothalamo-pituitary-adrenal axis activation: studies in Brattleboro rats. 1646 84

Desmopressin (DDAVP) is a well tolerated and convenient haemostatic agent that can be used in a number of clinical conditions with bleeding diathesis. It has several effects on the haemostatic system, causing endogenous release of coagulation factor VIII, von Willebrand factor and tissue-type plasminogen activator, among others. In this review we present a growing body of evidence showing that DDAVP treatment may impair spread of cancer cells and contribute to encapsulation of tumour tissue. Our data in preclinical animal models suggest a potential application of DDAVP in the perioperative management of aggressive solid tumours. Novel vasopressin analogues with improved antitumor effects are currently in development.
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PMID:Desmopressin and other synthetic vasopressin analogues in cancer treatment. 1651 12

In the study, the role of PKC and Ca++ in vasopressin regulation of the plasma membrane water permeability was studied in the cells of the mouse kidney collecting duct. Coefficient of osmotic water permeability of total cell surface (Pf) was calculated from the initial rate of cell swelling following the osmotic shock caused by changing the medium osmolarity from isotonic to hypotonic (300 mOsm to 200 mOsm). Desmopressin (dDAVP 1 nM) increased the Pf in hydrated mice from 168.4 +/- 11.8 microm/s up to 231.3 +/- 14.7 microm/s. The Ca++ chelator BAPTA prevented the desmopressin-induced increase in water permeability. Inhibition of PKC (Ro-31-8220 0.1 microM) also abolished the desmopressin-stimulated increase of plasma membrane water permeability, whereas inhibitor of PKC alone did not suppress the stimulation of the water permeability by db-cAMP. The PKC activity and calciumdependent second messengers seem to be important for regulation of water permeability by vasopressin.
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PMID:[Calciumdependent mechanisms in vasopressin regulation of osmotic water permeability in the mouse kidney collecting duct cells]. 1686 92

Desmopressin (DDAVP) is a synthetic vasopressin analog capable of inducing an increase in the plasma levels of von Willebrand factor and coagulation factor VIII. DDAVP has been used during surgery to prevent bleeding in patients with coagulation defects. We have previously demonstrated that adjuvant perioperative DDAVP therapy inhibits lung and lymph node metastasis in a breast cancer model. Here the effect of DDAVP on experimental lung colonization of B16 melanoma cells was investigated in a transgenic mice model with high levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) in the systemic circulation. Transgenic C57BL/6j-CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse albumin promoter/enhancer were employed. Treatment with DDAVP (2 microg/kg/dose) at the time of intravenous injection of B16 cells significantly inhibited the formation of lung metastases in TIMP-1 transgenic animals (p = 0.021), while no significant effect was obtained in control hybrid mice. The inhibition was not due to direct cytotoxic effects of DDAVP on tumor cells and no expression of vasopressin receptors was detected in B16 cells. Our data indicate that DDAVP therapy may impair successful implantation of circulating melanoma cells and suggest that high levels of circulating TIMP-1 display a cooperative role in the antitumor activity of the compound.
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PMID:Desmopressin reduces melanoma lung metastasis in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1. 1720 83


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