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)

Non-enzyme fibrinolytic agents include pharmacological agents which are active in vivo but inactive in vitro and synthetic chemical compounds which when added to blood or plasma in vitro directly induce fibrinolysis. There are a number of drugs with a short duration of action such as adrenalin, nicotinic acid, vasopressin and histamine. Vasoactive drugs probably act by stimulating the liberation of vascular activator. The effect of nicotinic acid is rapidly exhausted when injections are repeated. By contrast, the biguanides and certain anabolic steroids are capable of exerting a long term stimulation of endogenous fibrinolysis. Amongst these substances, phenformin, metformin, ethyloestrenol, stanozolol and a new substance, moroxydine chloride, have been studied. The biguanides appear to be capable of exerting an effect upon the synthesis and liberation of plasminogen vascular activator. The combination of an anabolic steroid and a biguanide would appear to be the most powerful. These various drugs have been used with success in cases of recurrent venous thrombosis in patients with an abnormally low level of plasminogen activator in the venous walls and/or low fibrinolytic activity after venous stasis. Chemical fibrinolytic agents were studied only in vitro, since the use of these substances in human therapeutics would seem to be still difficult in view of the fact that they are active only in a narrow range of concentrations.
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PMID:[Non-enzymatic fibrinolytic agents]. 3 Nov 13

Effects of vasopressin, its C-terminal fragments and derivatives on the system of hemostasis were studied in rats. Modification of amino acid sequence in vasopressin molecule led to distinct alterations in main peptide properties. Presence of ring structure in the peptide molecule appears to be obligatory to increase the content of factor VIII in blood, while absence of glycine in side chain caused a decrease in the rate of fibrinolysis and in activity of plasminogen activators.
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PMID:[Structure-activity determination of physiological reactions of vasopressin and its analogs on the hemostasis system]. 144 Dec 93

We describe two families with heterozygous plasminogen deficiency. In the first the patient was a 27 year-old female who suffered an acute episode of ischemic cerebrovascular disease affecting the left temporal lobe documented by arteriographic, gammagraphic and CAT studies. She had no family history of thrombotic conditions. In the other family the propositus was a 31 year-old man with spontaneous deep venous thrombosis in the left leg. His father was also symptomatic, with a history of recurrent thrombotic complications after predisposing factors, that included multiple venous thrombosis and a pulmonary embolism. Laboratory data showed normal hemostasis test results. Antigenic and functional levels of protein C, protein S and antithrombin III were within normal limits. The only abnormality found was decreased plasminogen activity in plasma; antigenic and functional levels were reduced to about half-normal levels. In both cases crossed immunoelectrophoresis revealed a normal migration pattern of plasminogen. Thus, we conclude that our patients were carriers of congenital hypoplasminogenemia or familial type I plasminogen deficiency, due to decreased synthesis. We also reported on fibrinolytic response to infusion of DDAVP, a synthetic analogue of the antidiuretic hormone. Fibrinolytic activity was normal in basal conditions as well as in response to DDAVP infusion.
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PMID:[Plasminogen deficiencies in 2 Spanish families. Response to the administration of DDAVP]. 236 94

Participation of central and peripheral++ cholinoreceptors in responses of blood coagulation system to intravenous vasopressin injection has been studied in experiments on white rats. Vasopressin was injected in combination with atropine and metacine Intensification of the procoagulant activity, that was observed 15 min after vasopressin injection (4 micrograms/kg), was practically retained during cholinergic blockade. The intensification of fibrinolytic activities as a result of an increase in the level of plasminogen activators in blood, is to a great extent blocked by atropine rather than by metacine. Consequently, to intensify the procoagulant activity without changes in fibrinolysis (for example hemophilia) it is necessary to use the vasopressin injection in combination with atropine.
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PMID:[The role of cholinergic receptors in the reactions of the hemostasis system to vasopressin]. 259 88

Some patients with von Willebrand's disease do not respond to stimuli such as venous occlusion and infusion of a vasopressin analogue DDAVP. In these patients, fibrinolytic activity is not enhanced and von Willebrand's factor is not released into the blood. Skin biopsies and cryostat sections were used to study the fibrinolytic activity of skin vessels and localization of tissue plasminogen activator (t-PA) in three patients with severe form of von Willebrand's disease. On fibrin films, no fibrinolysis developed around the skin vessels of the patients; however, using specific polyclonal and monoclonal antibodies to t-PA, and peroxidase coupled specific IgG, presence of t-PA antigen was demonstrated in endothelial cells (EC) of all of them. In plasma no t-PA activity was detected either before or after venous occlusion although t-PA inhibitor activity was in a normal range. Small amounts of t-PA antigen was measured in blood by ELISA. From these results, it is concluded that in patients with severe forms of von Willebrand's disease, t-PA present in EC is not functional and can not transform plasminogen into plasmin.
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PMID:Absence of functional activity of tissue plasminogen activator in patients with severe forms of von Willebrand's disease. 311 91

Plasminogen activators are highly selective proteases that activate the proenzyme plasminogen to the general protease, plasmin. We studied a porcine kidney cell line, originally isolated as a high producer of plasminogen activator, in which activities of cellular adenylate cyclase and cAMP-dependent protein kinase are increased in response to calcitonin. We found that salmon calcitonin, in the concentration range 0.03-300 nM, increased plasminogen activator production up to approximately 1,000-fold and concurrently inhibited cell multiplication; both of these effects were reversible. Human calcitonin was approximately 0.01 times as potent as salmon calcitonin, corresponding to potency differences observed in other biological systems. Plasminogen activator production was also stimulated by other agents that raise cellular cAMP levels such as cholera toxin, phosphodiesterase inhibitors, and vasopressin, but not to the same extent as by calcitonins. The rapidity and sensitivity of the plasminogen activator determination and other cellular responses may make it possible in the future to use this cell stain in a convenient bioassay for calcitonins and their analogues.
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PMID:Calcitonin stimulates plasminogen activator in porcine renal tubular cells: LLC-PK1. 627 91

Plasminogen can be activated by intrinsic activators that circulate in plasma in a precursor form, by extrinsic activator originating from tissues or the vessel wall and by the exogenous activators, urokinase and streptokinase. Tissue activator and vascular activator are probably identical. Dialysis of plasma against pH 4.0 buffer causes denaturation of the plasmin inhibitors, alpha 2-antiplasmin and C1-inhibitor, while alpha 2-macroglobulin is left intact. Incubation of pH 4.0-pretreated plasma with urokinase or streptokinase at pH 7.5 led to activation of plasminogen and prorenin. Incubation of a plasma fraction, which contained plasminogen and prorenin but no alpha 2-antiplasmin and renin, with highly purified tissue plasminogen activator also led to activation of prorenin. The vasopressin analogue, 1-desamino-8-D-arginine vasopressin (DDAVP), is a potent stimulant for the release of extrinsic activator into the bloodstream. After infusion of DDAVP, 0.4 micrograms/kg, into normal subjects, parallel increments in plasma fibrinolytic activity and renin were observed. Infusion of DDAVP into patients with type IV hyperlipoproteinaemia had little effect on plasma fibrinolytic activity and the response of plasma renin was also subnormal. These observations warrant further studies on a possible role for plasminogen activators in prorenin activation in vivo.
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PMID:Activation of plasma prorenin by plasminogen activators in vitro and increase in plasma renin after stimulation of fibrinolytic activity in vivo. 675 94

Angiotensin II (AII)- and Arg8-vasopressin (AVP)-regulated gene expression in vascular cells has been reported to contribute to vascular homeostasis and hypertrophy. In this report, AVP-induced expression of plasminogen activator inhibitor (PAI)-2 mRNA in rat microvessel endothelial (RME) cells was identified using differential mRNA display. Further characterization of vasoactive peptide effects on PAI expression revealed that AII stimulated a 44.8 +/- 25.2-fold and a 12.4 +/- 3.2-fold increase in PAI-2 mRNA in RME cells and rat aortic smooth muscle cells (RASMC), respectively. AII also stimulated a 10- and 48-fold increase in PAI-1 mRNA in RME cells and RASMC, respectively. These AII effects were inhibited by either Sar1, Ile8-angiotensin or the AT1 antagonist DuP 735, but were not significantly altered in the presence of the AT2 antagonist PD123319. AII stimulation of RASMC and RME cells also significantly increased both PAI-1 protein and PAI activity released to the culture medium. Inhibition of protein kinase C completely blocked PMA-stimulated induction of PAI-2 mRNA in both cell types and inhibited the AII-stimulated increase in RASMC by 98.6 +/- 2.8%. In contrast, protein kinase C inhibition only partially decreased the AII-stimulated PAI-2 expression in RME cells by 68.8 +/- 11.1%, suggesting that a protein kinase C-independent mechanism contributes to a 6.9 +/- 1.5-fold AII induction of PAI-2 expression in endothelial cells. AII and PMA also stimulated protein tyrosine phosphorylation in RME cells, and the tyrosine kinase inhibitor genistein partially blocked their induction of PAI-2 mRNA. These findings suggest that AII may regulate plasminogen activation in the vasculature by inducing both PAI-1 and PAI-2 expression.
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PMID:Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. 788 82

Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.
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PMID:Repeated infusions of DDAVP induce low response of FVIII and vWF but not of plasminogen activators. 832 82

The increase in blood clotting factor VIII (antihaemophilic factor, F-VIII) and fibrinolytic activity induced by the administration of neurohypophyseal hormone analogues, was assayed in sheep. Peptides with high selectivity for vasopressin V1, V2 or myometrial oxytocin receptors in the dose range of 0.1-10 micrograms/kg body weight were investigated. The main conclusions are as follows. The time-course of the F-VIII plasma levels following the administration of the peptides was biphasic, with one surge at about 20 min, a rebound phase, and another increase with the maximum at 60-90 min. The time-course of the fibrinolytic response, expressed as biological activity of plasminogen activator in the plasma euglobulin fraction, displayed a single maximum within 60 min. The baseline responses were reached within 90-120 min. Responses were expressed as integrals of the time-concentration curves in a predetermined time range (90-120 min). F-VIII and plasminogen activator enhancing effects seemed to be tightly linked to the specific vasopressin V2 receptor activities. [Val4,D-Arg8]Vasopressin displayed higher plasminogen activator activities than the standard substance, deamino[D-Arg8]vasopressin. The vasotocin analogue [Phe2,Orn8]oxytocin, a specific vasopressin V1 receptor agonist, also displayed high antihaemophilic and fibrinolytic potencies, expressed in terms of ED50 values, but did not reach the same maximal response as vasopressin V2 receptor agonists. Oxytocin and its highly selective uterotonic analogue, [Thr4,Gly7]oxytocin, displayed low antihaemophilic, and virtually no plasminogen activating potencies. Surprisingly, vasopressin V2 and V1V2 receptor antagonists studied in our experiments showed both enhanced F-VIII and fibrinolytic responses. Dose-response curves frequently displayed a decrease of the F-VIII, and sometimes also decreased fibrinolytic responses, at higher peptide doses. Strong decreases of the packed cell volume (haematocrit) and somewhat lower decreases of the total plasma protein concentration were observed shortly after administration of the peptides.
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PMID:Effects of neurohypophyseal hormone analogues on blood clotting factor VIII and fibrinolytic activity in sheep. 912 40


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