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

More than 20 years following the recognition of a possible role for eicosanoids in ovarian function a physiological role for prostaglandins and/or leukotrienes in human ovulation, corpus luteum function and tubal motility remains to be demonstrated. With respect to ovarian function, the well-characterized preovulatory rise in eicosanoid production in animal species and humans, in conjunction with the large body of experimental evidence employing inhibitors of prostaglandin synthesis and replacement of individual prostaglandins, has provided strong evidence for a role in follicular rupture independent of other LH-mediated ovulatory events. The possible mechanism of prostaglandin-induced follicle rupture may involve stimulation of proteolytic activity via substances such as plasmin and PA; however, this is controversial. A role for prostaglandins in ovarian luteal function is well established in laboratory animals and large ruminant species, where PGF2 alpha derived from the uterus has been demonstrated to be the luteolytic factor. In humans, luteal function may be influenced by local intraovarian eicosanoid production, which has been suggested to involve the paracrine interaction of local ovarian hormones such as oxytocin, noradrenaline, insulin and IGFs, to name but a few. Several lines of evidence have also implicated prostaglandins as an aetiological factor in ovarian pathological states such as seen in the OHSS. However, the bulk of clinical experimental evidence to date has failed to support this contention. Prostaglandin production has likewise been well characterized in the fallopian tube in both humans and animal species. Whereas a role for prostaglandins in tubal transport has been demonstrated with animal species such as the rabbit, several studies have failed to define a similar function in humans. More recently, direct injections of prostaglandin analogues into the fallopian tube and the corpus luteum have been shown to be efficacious as a treatment for ectopic pregnancy. Whether the primary mechanism of action involves effects on tubal musculature or corpus luteum function, or is simply a local vascular effect, remains to be demonstrated. Therefore, although the physiological role for eicosanoids in ovarian and tubal function remains unclear, particularly in the human, an increasing body of recent evidence has suggested an important paracrine function for this class of cellular mediators whose interaction with other more recently characterized local ovarian factors has only begun to be recognized.
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PMID:Prostaglandins in the ovary and fallopian tube. 147 96

The effect of the neuropeptide oxytocin, administered i. m., on the state of fibrinolysis and the kallikrein-kinin system was studied throughout an experiment on 88 Wistar albino nonpregnant female rats. Oxytocin was shown to cause fibrinolytic activation as a result of the elevated activity of the plasmin enzyme, plasminogen activators and the suppressed activity of antiplasmins. At the same time oxytocin stimulated the activity of the kallikrein-kinin system as was seen from the reduced level of serum kallikreinogen and the increased level of kallikrein.
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PMID:[Effect of oxytocin on fibrinolysis and the status of the kallikrein-kinin system]. 274 Mar 21

Exogenous daily oxytocin injections given immediately before milking increase milk production. To investigate the mechanism by which oxytocin increases milk production, oxytocin injections were given before and after milking, and saline injection was given before milking as a control. The experimental design was a replicated Latin square; two complete trials were performed: one with 12 cows (45 d) and another with 15 cows (95 d). In the first trial, the least squares means of milk production were 29.2, 29.3, and 28.3 kg for oxytocin injection before milking, oxytocin injection after milking, and saline injection before milking, respectively. In the second trial, the least squares means of milk production were 33.3, 32.9, and 32.4 kg for oxytocin injection before milking, oxytocin injection after milking, and saline injection before milking, respectively. Oxytocin before and after milking significantly increased milk production by 3%. The results suggest that increases in milk production may not be caused by removal of residual milk but by increased gland output of milk. The effect on milk plasmin activity, fat, protein, SCC, and lactose was nonsignificant and may indicate that effect of oxytocin is not manifested through an effect on cell remodeling.
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PMID:The effects of daily oxytocin injections before and after milking on milk production, milk plasmin, and milk composition. 832 28

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

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

Amniotic Fluid Embolism (AFE) is a rare obstetric catastrophe that occurs in approximately 1/50,000 pregnancies and has a mortality rate in excess of 80%. AFE is a condition that is poorly understood and often difficult to diagnose. We report a case of a healthy 27-yr-old gravid two, 35 wk gestation parturient with a previous Cesarean section two years previously, and presently admitted for emergent Cesarean section due to premature uterine contractions. Induction of general anesthesias was performed with no problem and a male preterm infant with Apgar 8 at 1 min was delivered. Amniotic fluid was bloody and 40% placental abruption existed. Following delivery of the placenta, patient suddenly became plethoric and O2 saturation began to decrease and no pulse could be palpated! Immediate CPR was successful but she was hemodynamically unstable and signs of right heart strain was obvious. Right jugular venous catheterization was performed, vasopressors were administered. After a two hours period of relatively stable vital signs, patient's reflexes returned to normal, however, profound coagulopathy on lab data was reported and she was treated with 10 unit Packed Red Blood Cells (PRBCs), 10 unit FFP and 8 unit platelets, Sodium bicarbonate, oxytocin and Methergine. The patient remained hemodynamically unstable while laparotomy-hysterectomy was performed to stop the bleeding. Unfortunately attempts were unsuccessful and patient died four hours later in ICU. Post-mortem findings showed signs of Disseminated Intravascular Coagulation (DIC), no fetal squamous cells in pulmonary vasculature were found and special staining of Cytokeratin marker shows no positive cells in lumen of vessels. The post-mortem diagnosis of AFE is challenging to forensic investigators and pathologists and can be confirmed by histological confirmation of amniotic fluid contents in the pulmonary vasculature, although they may be difficult to identify. In recent years it has been suggested that AFE is an anaphylactoid reaction to fetal antigens and an elevated serum tryptase level is increasingly being used to support the diagnosis. Sudden onset of cardiovascular collapse and early signs of right heart strain and fulminant DIC supports the diagnosis of AFE in this case, although no fetal debri could be find in pathologic staining.
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PMID:Sudden cardiac arrest during cesarean section -- a possible case of amniotic fluid embolism. 1958 89