Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a variety of peptide analogues of oxytocin (OT) and Arg8-vasopressin (AVP), OT-mediated induction of urokinase-type plasminogen activator (uPA) was examined in LLC-PK1 renal epithelial cells, which possess distinct high-affinity receptors of both the OT- and vasopressin renal (V2-) types. OT or OT-receptor specific agonists induced concentration-dependent cAMP synthesis, activation of the cAMP-dependent protein kinase (cAMP-PK) and uPA production consistent with their respective binding affinities for the V2- and not the OT-receptor. OT-mediated uPA induction could be inhibited in a concentration-dependent fashion by coincubation with a V2/V1-receptor specific antagonist, but not by an OT-receptor specific antagonist. Results implied that stimulation of cAMP- and uPA responses in LLC-PK1 cells by OT was V2-receptor-mediated.
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PMID:Oxytocin induced cAMP-dependent protein kinase activation and urokinase-type plasminogen activator production in LLC-PK1 renal epithelial cells is mediated by the vasopressin V2-receptor. 838 Feb 70

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

[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 hypothalamo-neurohypophysial system (HNS), synthesizing arginine vasopressin (AVP) and oxytocin (OXT), is well known to show structural plasticity during chronic physiological stimulation such as salt loading and lactation. In the present study, we undertook in the HNS to study localization and activity-dependent changes in the expression of matrix-degrading enzymes such as tissue plasminogen activator (tPA) and matrix metalloprotease-3 (MMP-3). Double labeling confocal microscopy demonstrated that the immunoreactivity of tPA was localized at AVP-positive dendrites in the supraoptic nucleus (SON) and AVP-positive terminals in the neurohypophysis (NH). The immunoreactivity of tPA was also seen at astrocytic processes in the HNS. Likewise, the immunoreactivity of MMP-3 was observed at AVP-positive dendrites and terminals. High magnification observation further revealed punctate distribution of tPA and MMP-3 immunoreactivity at dendrites and terminals, suggesting that they are localized at neurosecretory granules. Salt loading, known as the chronic stimulation to cause the structural plasticity, increased protein and mRNA levels of tPA in the SON but reduced protein levels of it in the NH. The chronic stimulation also increased protein levels of urokinase plasminogen activator in the SON, but the stimulation did not change protein levels of MMP-3 in the SON and NH. Depolarizing agent KCl released tPA from isolated neurosecretosomes, and this depolarization-dependent release was abolished by verapamil, a Ca(2+) channel blocker. These results demonstrate that tPA and MMP-3 are localized mainly at dendrites and terminals of AVP-expressing magnocellular neurons and tPA is released in an activity-dependent manner, suggesting that matrix-degrading proteases are candidate molecules to be concerned with the structural plasticity in the HNS.
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PMID:Matrix-degrading enzymes tissue plasminogen activator and matrix metalloprotease-3 in the hypothalamo-neurohypophysial system. 1615 Apr 23

We examined the effects of the neuropeptide hormones vasopressin and oxytocin, and their respective synthetic derivatives desmopressin and isotocin, on F3II mouse mammary carcinoma cells. Vasopressin and desmopressin at concentrations ranging from 0.1 to 1 mu M were mitogenic for F3II cells and induced protein accumulation. On the contrary, oxytocin and isotocin were moderately growth inhibitory at similar doses. In confluent monolayers vasopressin stimulated the secretion of urokinase, a profibrinolytic enzyme involved in hematogenous metastasis. However, the net effect of the peptide on tumor-derived proteolytic activity was dependent on cell density. Stimulation of cell growth and urokinase production by vasopressin was strongly linked with calcium mobilization. These data suggest that vasopressin and its synthetic analog desmopressin may be important modulators of the behavior of metastatic mammary tumor cells.
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PMID:Modulation of growth and urokinase secretion by vasopressin and closely related nonapeptides in metastatic mouse mammary tumor cells. 2153 87