UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analyzed the plasminogen activator (PA) content of normal rodent mammary glands at different stages of the mammary life cycle and after exposing the animals to various hormones; we have also assessed the PA response of mammary explants to a variety of hormonal environments. Similar studies were performed on a limited number of primary mammary tumors. Plasminogen activator production was clearly correlated with mammary involution. A large but transient increase in enzyme content followed the initiation of involution in all glands, and the enzyme was produced by mammary cells, not by macrophages or granulocytes. Oxytocin, prolactin and hydrocortisone, which slowed or blocked involution, produced parallel effects on gland regression and PA synthesis. PA synthesis by explants in organ culture was induced by hormonal environments that fostered involution and repressed by those that promoted lactation. Mammary tumors produced much more PA than normal tissue both in vivo and in vitro, and distinct differences were found in the response of enzyme synthesis to hormones. The results reinforce the association of PA with tissue remodeling; show that the enzyme can be used as an indicator of cellular response to a wide range of hormones in both normal and malignant tissue; and suggest that observations of this type in organ culture may be of some value in predicting physiological responses in vivo.
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PMID:Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. 45 56

The influence of substances known as low molecular weight mediators such as biogenic amines, peptides and prostaglandins on the plasminogen activator release was studied in the isolated perfused pig ear. Among the substances tested, histamine and the plasma kinins bradykinin and kallidin were found to possess a dose-dependent activator-releasing effect, which in case of histamine can be suppressed by an antihistamine (promethazine). Serotonin and the prostaglandins at concentrations up to 10(-5)M possess no significant activator-releasing effect. Compared with the biogenic peptides angiotensin, oxytocin, vasopressin, and eledoisin, only the latter was found to release plasminogen activator. Studies on the influence of the substances tested on the capillary permeability showed that enhanced permeability is caused only by those mediators which cause also increased activator release.
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PMID:[Influence of mediators on plasminogen activator release]. 75 12

Because timing of sampling is crucial in an investigation of the effects of labor and delivery on fibrinolysis we conducted a study of fibrinolytic markers in plasma of 10 healthy multiparous women in whom labor was induced, which allowed standardization of sampling times in relation to the course of labor and delivery. Blood samples were taken 5 min before the start of oxytocin infusion, at full cervical dilatation, and within 5 min after delivery of the placenta. A sample of mixed free flowing cord blood was obtained after delivery with the placenta in situ. Variables determined were tissue-type plasminogen-activator (t-PA) and the plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). The only significant change between the beginning of the induction of labor and the end of the first stage of labor was a rise in t-PA antigen (P = 0.01). All variables, except PAI-2 antigen, changed significantly after delivery of the placenta: t-PA antigen and activity showed a rise (P < 0.05), accompanied by a fall in PAI-1 antigen and activity (P < 0.01). T-PA activity in cord plasma was higher (P < 0.01) in comparison with maternal plasma concentrations at the end of the first stage of labor, t-PA antigen levels were similar, and PAI-1 antigen and activity and PAI-2 antigen were lower in cord plasma (P < 0.001). Our study shows that activation of the maternal fibrinolytic system can already be detected during labor, with a marked further increase in fibrinolytic potential after placental separation.
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PMID:Effects of labor and delivery on fibrinolysis. 795 59

Current hypotheses suggest that the degradation of cervical collagen and elastin leads to cervical effacement and dilation during labor. The collagenolytic activity is thought to be initiated through the conversion of latent (pro)collagenase to active collagenase by the plasmin formed from plasminogen or by other proteases similarly formed from their inactive zymogens. We presently demonstrate that meperidine stimulates the activity of several enzymes in the proteolytic cascade leading toward proteolysis of connective tissue proteins. Meperidine in its therapeutic concentration range produces a 26% stimulation of urokinase activity on substrate S-2444, a 39% stimulation of plasmin activity on substrate S-2551, and a 33% stimulation of collagenase activity on 14C-labeled globin substrate. These direct effects on the enzyme activities are noted in vitro with the purified enzymes and were confirmed with several small molecular weight chromogenic substrates and with 14C-globin protein substrate. Oxytocin at levels found during active labor fails to stimulate the in vitro activity of purified urokinase, plasmin, collagenase, trypsin, or tissue-type plasminogen activator. The effect of meperidine on the proteolytic enzymes suggests that its ability to promote cervical effacement and distention during labor may be at least partially due to a meperidine-induced stimulation of cervical proteases.
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PMID:Direct stimulation of urokinase, plasmin, and collagenase by meperidine: a possible mechanism for the ability of meperidine to enhance cervical effacement and dilation. 847 75

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

The synthetic arginine vasopressin (AVP) analog 1-desamino-8-D-arginine vasopressin (DDAVP) is used in a variety of hemorrhagic disorders. The present experiments were designed to further characterize the mechanism of DDAVP-induced release of hemostasis factors. The [3H]AVP-labeled AVP receptor in canine renomedullary membranes exhibited an AVP V2 profile because the V2 receptor agonist DDAVP displayed similar subnanomolar affinities as the natural hormone AVP, whereas the two selective V1a compounds SR 49059 and d(CH2)5Tyr(Me)AVP as well as the selective V1b agonist D-Pal and oxytocin were much less potent. The rank order of the binding affinities of three V2 receptor antagonists was SR 121463 (a newly described selective V2 receptor antagonist) > OPC 31260 >> d(CH2)5D-Ile2,Ile4AVP. In conscious dogs, DDAVP (0.1-1 microg/kg I.V.) caused a dose-related increase (maximum, 43-52% at 30 min) in plasma levels of factor VIII (FVIII), von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA), but not in levels of plasminogen activator inhibitor-1. A DDAVP-induced hemostasis factor release was also observed in bilaterally nephrectomized dogs. Pretreatment with SR 121463 inhibited DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels in a dose-dependent manner (ID50 = 14.0 +/- 4.0, 12.4 +/- 3.0 and 16.7 +/- 1.0 microg/kg I.V., respectively). OPC 31260 (300 microg/kg I.V.) revealed a lower activity than SR 121463, and d(CH2)5[D-Ile2,Ile4]AVP (30 microg/kg I.V.) was without effect on the DDAVP response. Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels. The present results, therefore, strongly suggest that the effect of DDAVP on hemostasis factors occurs via a specific interaction with extrarenal V2 receptors.
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PMID:V2 receptor antagonism of DDAVP-induced release of hemostasis factors in conscious dogs. 926 20

Tumor necrosis factor alpha (TNFalpha) has been shown to be a potent stimulator of prostaglandin (PG) F(2alpha) secretion in the bovine endometrium. The aims of the present study were to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGF(2alpha) in response to TNFalpha, and the intracellular mechanisms of TNFalpha action. Cultured bovine epithelial and stromal cells were exposed to TNFalpha (0.006-6 nM) or oxytocin (100 nM) for 4 h. TNFalpha resulted in a dose-dependent increase of PGF(2alpha) production in the stromal cells (P < 0.001) but not in the epithelial cells. On the other hand, oxytocin stimulated PGF(2alpha) output in the epithelial cells but not in the stromal cells. When the stromal cells were incubated for 24 h with TNFalpha and inhibitors of phospholipase (PL) C or PLA(2), only PLA(2) inhibitor completely stopped the actions of TNFalpha (P < 0.001). When the stromal cells were exposed to TNFalpha and arachidonic acid, the action of TNFalpha was augmented (P < 0.001). When the stromal cells were incubated for 24 h with a nitric oxide (NO) donor (S-NAP), S-NAP stimulated the PGF(2alpha) production dose-dependently. Although an NO synthase (NOS) inhibitor (L-NAME) reduced TNFalpha-stimulated PGF(2alpha) production, an inhibitor of phosphodiesterase augmented the actions of TNFalpha and S-NAP (P < 0. 05). The overall results indicate that the target of TNFalpha for stimulation of PGF(2alpha) production in cattle is the endometrial stromal cells, and that the actions of TNFalpha are mediated via the activation of PLA(2) and arachidonic acid conversion. Moreover, TNFalpha may exert a stimulatory effect on PGF(2alpha) production via the induction of NOS and the subsequent NO-cGMP formation.
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PMID:Production of prostaglandin f(2alpha) by cultured bovine endometrial cells in response to tumor necrosis factor alpha: cell type specificity and intracellular mechanisms. 1077 56

We have previously described the presence of the functional plasminogen activator system on the surfaces of bone neoplastic cells and the fact that plasmin specifically cleaves bone matrix protein osteocalcin (OC). The cleavage of OC to NH2-midterminal (1-44) and COOH-terminal RFYGPV hexapeptide (44-49) proceeds with detachment of both products from bone mineral. Because the sequence of OC-derived hexapeptide (HP) is nearly identical to the E2 region of the oxytocin receptor (OTR), we set out to ascertain whether the HP interferes with the osteosarcoma (OS)-associated oxytocin (OT) system. We documented the presence and functional activity of OTRs in several OS cells by means of (a) OT-mediated inhibition of OS growth; (b) expression of OTR mRNA by means of reverse transcription-PCR; (c) immunofluorescence staining with IF3 monoclonal antibody specific for human OTR; and (d) saturation binding and Scatchard analysis of OT binding to the receptors of isolated membranes or intact OS cells. Although we could not demonstrate direct binding of HP to OT, the presence of HP in cultures of OS cells antagonizes the inhibitory effect of OT on these cells. Additionally, in competitive binding assays, the HP effectively competes with binding of OT to its cognate receptors. The results indicate the existence of an OTR/OT system in tumor cells of bone origin. Suggested plasminogen activator-OC-OTR/OT interactions may have an effect on the regulation of cell proliferation within the bone tissue as well as properties of the extracellular matrix surrounding the tumor foci in the bone.
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PMID:A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth inhibition [corrected] of osteosarcoma cells. 1091 58

[deamino-Cys(l),d-Arg(8)]-vasopressin (dDAVP), known to be an arginine vasopressin (AVP) V(2) receptor agonist, is an agent that increases fibrinolytic activity levels in plasma after its infusion into the human body. However, mechanisms underlying an increase and exact localization of the extrarenal dDAVP-responsive V(2) receptor remain unclarified. Two AVP receptors, V(1a) and V(2), and a related oxytocin (OT) receptor were found to be expressed in human lymphocytes. Furthermore, we found an increase of fibrinolytic activity in the medium of peripheral lymphocytes obtained from human volunteers less than 20 min after dDAVP infusion. The increased activity was also detected in the medium after incubating the lymphocytes in the presence of dDAVP in vitro, being highest at 20 min after the incubation. In accord with the increased fibrinolytic activity, the levels of urokinase-type plasminogen activator (uPA) in the medium were also increased. However, there was no significant difference of plasminogen activator inhibitor-1 (PAI-1), pro-uPA, and tissue-type plasminogen activator (tPA) concentrations in the medium between dDAVP treatment and control. When lymphocytes were preincubated with a V(2) receptor antagonist [Adamantaneacetyl(1),O-Et-d-Tyr(2),Val(4),Aminobutyryl(6),Arg(8,9)]-vasopressin, the dDAVP-induced uPA increase was diminished. In contrast, preincubation with a V(1) receptor antagonist, [beta-Mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin, prior to dDAVP treatment resulted in a greater increase of the uPA concentration in the medium than with the dDAVP treatment alone. Thus it was suggested that dDAVP may induce uPA release from human lymphocytes via V(2) receptor-mediated reaction, and also via cross-talk between V(1) and V(2) receptors.
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PMID:Induction of uPA release in human peripheral blood lymphocytes by [deamino-Cysl,D-Arg8]-vasopressin (dDAVP). 1519 31

The release of arachidonic acid from membrane glycerophospholipids through the action of phospholipases (PLs) is the first step in the biosynthesis of prostaglandins (PGs). In reproductive tissues, the most important PLs are cytosolic PLA(2) (cPLA(2)) and types IIA and V of the secretory isoform (sPLA(2)). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA(2) activity and expression during pregnancy and labor. The activity of sPLA(2) increased near labor, whereas cPLA(2) activity augmented towards the end of gestation. The levels of sPLA(2) IIA and cPLA(2) mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA(2) V mRNA was not regulated during pregnancy. The administration of atosiban (synthetic OT antagonist) together with tamoxifen (antagonist of estrogen receptors) was able to decrease cytosolic and secretory PLA(2) activities, diminish the expression of sPLA(2) IIA and cPLA(2), as well as decrease PGF(2 alpha) production before the onset of labor (P<0.01). The ovarian steroid did not affect PLA(2) during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17beta-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA(2), thus controlling PGF(2 alpha) synthesis prior to the onset of labor.
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PMID:Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor. 1766 Feb 44

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