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)

Endothelins 1, 2 and 3 (ET-1, ET-2 and ET-3; 1-30 nM) caused long-lasting concentration-dependent tonic contractions of uterine strips from non-pregnant rats. The potency of ET-1 (EC50 7 nM) was similar to that of angiotensin II (AII) and greater than that of ET-2 or ET-3 (EC50S greater than or equal to 10 nM), bradykinin, Bay K 8644, oxytocin (OT), 5-hydroxytryptamine, prostaglandin F2 alpha (PGF2 alpha) or acetylcholine. Strips from 21-day pregnant rats were 2- to 3-fold more sensitive to ET-1, AII, OT and PGF2 alpha and 200-fold more sensitive to Bay K 8644 than non-pregnant preparations. The development of tonic responses to ET-1 (30 nM) and of phasic-rhythmic ones to Bay K 8644 (300 nM) was fully prevented in strips from non-pregnant rats bathed in Ca2(+)-free medium, but stepwise reintroduction of Ca2+ (0.03-3 mM) to the solution allowed the manifestation of contractions in response to both agonists. Responses to ET-1 required less Ca2+ than those to Bay K 8644. Strips challenged with ET-1 while in Ca2(+)-free medium developed greater contractions upon reintroduction of Ca2+ than preparations stimulated with the peptide in normal medium. The reverse occurred with Bay K 8644-induced contractions. Nicardipine (10 nM) abolished the responses of strips from non-pregnant rats to Bay K 8644 (300 nM), but only attenuated ET-1-induced (30 nM) contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of endothelins, Bay K 8644 and other oxytocics in non-pregnant and late pregnant rat isolated uterus. 171 Jan 86

Immunoreactive endothelin-1 (IR-ET-1) was detected in the cultured medium from endometrial but not myometrial cells of rabbits in primary culture using a specific radioimmuno assay (RIA). Similar results were obtained with a radioreceptor assay using myometrial membranes. In a reverse-phase HPLC synthetic ET-1 and IR-ET-1 of the extract medium from endometrial cells revealed essentially the same elution profiles, as determined by RIA. Two selective agonists of oxytocin (OT) or V1 vasopressin (VP) receptors produced, respectively, a 6- and 2-fold increase of IR-ET-1 release from endometrial cells. These effects were completely reversed by the addition of two specific antagonists of OT and V1 VP receptors. Our results indicate that ET-1 is produced and released in the culture medium of rabbit endometrial cells in primary culture. The release of ET-1 is under receptor-specific control by neurohypophyseal hormones.
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PMID:Neurohypophyseal hormone regulation of endothelin secretion from rabbit endometrial cells in primary culture. 240 23

Endothelin (ET)-1, a neuropeptide and possible neuromodulator, has been found in the hypothalamic supraoptic and paraventricular nuclei (SON and PVN) of the rat in the distribution of oxytocin (OT) neurons. Within the hypothalamus of the pregnant rat, we investigated the developmental expression of the ET-1 gene and the possibility of coordinate expression of the ET-1 and OT genes. Blots containing hypothalamic mRNAs from 4-, 14-, 18-, and 21-day-old pregnant rats were hybridized to a 32P-labeled probe specific to the rat ET-1 gene. Hypothalamic tissue contained an ET-1 transcript of approximately 2.3 kb size. ET-1 mRNA abundance increased significantly in the SON and PVN from early to late gestation (P = 0.005 and 0.05, respectively). Blots containing hypothalamic mRNA were rehybridized to a 32P-labeled probe specific to exon C of the rat OT gene. OT gene expression increased significantly within both the hypothalamic SON (p = 0.0009) and PVN (P = 0.003) as gestation advanced. The sizes of the hypothalamic ET-1 and OT transcript sizes remained unchanged throughout gestation. Hypothalamic ET-1 and OT transcripts display stage-specific increases during gestation. ET-1 may be a neuroendocrine regulator of pregnancy-related events in the rat, and may act alone or in concert with OT.
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PMID:Expression of the endothelin-1 and oxytocin genes in the hypothalamus of the pregnant rat. 752 24

Endothelins (ETs) caused concentration-dependent contraction in pregnant rat myometrium. ET-2 was as potent as ET-1 in affecting contractile responses, whereas ET-3 was considerably less potent than ET-1 or ET-2. ETs also increased inositol phosphate (IP) production in a dose-dependent manner, with IP production paralleling the contractile response. The rank order of potency for both the contractile responses and IP production was ET-1 = ET-2 > ET-3. When we compared the important oxytocic agent oxytocin, we found that oxytocin (10(-7) M) strongly increased contractility and IP production, and the responses were comparable to those elicited by ET-1 (10(-7) M) and ET-2 (10(-7) M). These results suggest that ET-induced myometrial contraction involves phospholipase C activation, and that a subtype of endothelin receptor existing in pregnant rat myometrium could be classified as ETA.
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PMID:Effects of endothelins on mechanical activity and inositol phosphate production in pregnant rat myometrium. 763 52

To determine the intrauterine defensive role of urinary trypsin inhibitor (UTI), we studied the effects of UTI in amniotic fluid, fetal membranes and myometrium. The level of UTI was 94 +/- 34 U/ml in neonatal urine (compared to adult urine 8.0 +/- 6.0 U/ml) and 88 +/- 37 U/ml in amniotic fluid. This may indicate that the main source of UTI in the amniotic fluid is the fetal urine. UTI was found to be concentrated in vernix, fetal intestine, amniotic membranes and uterine myometrium. Immunostaining of term amnion revealed a dark staining for UTI, whereas in premature deliveries UTI staining was markedly decreased. In myometrium, the concentration of UTI was found to be increased during pregnancy compared to non pregnant myometrium. Also, placentas were well stained for UTI in term pregnancy. Thus UTI has an important role in amniotic fluid, fetal membranes, placenta and uterine muscles. UTI has an inhibitory effect on several enzymes and cytokines. UTI was found to inhibit neutrophil elastase activity as well as trypsin activity. Its inhibitory activity was increased in the presence of lipid. LPS stimulated amnion cells trapped more UTI than unstimulated amnion cells. UTI in amnion cells was released after addition of 1% meconium solution. UTI was also found to inhibit the effect of IL-1, TNF and interleukin-8 on amnion. These results indicate that UTI localized in amnion is important in the protection of fetal membrane especially against bacterial infections and cytokines. It is known that endothelin (ET), prostaglandin F2 alpha (PGF2 alpha) and oxytocin can induce uterine contraction. UTI could inhibit uterine contractions stimulated by ET, PGF2 alpha and oxytocin in isometric contraction test. UTI could also inhibit cervical maturation induced by interleukin-8. Therefore UTI is essential for maintenance of pregnancy. From the isometric contraction tests, we assumed that UTI might works through regulation of calcium entry or availability in the cells. Initial increase in intracellular calcium was also inhibited by UTI pre incubation dose dependantly. We examined the change in intracellular calcium at single cell level by digital image analysis with Fura 2AM as a calcium probe. At resting level UTI incubation did not produce any significant changes in intracellular free calcium. Thrombin, LPS, interleukin-8 and ET-1, known calcium agonists could increase intracellular calcium in fibroblasts, amnion and uterine myocytes. Whereas as the same doses of those known calcium agonists could not change the intracellular free Ca2+ concentrations in UTI pre incubated fibroblasts, amnion cells and uterine smooth muscle cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Intrauterine defensive mechanism of amniotic fluid and fetal membranes]. 808 4

This in vitro study was undertaken to investigate the effects of endothelin 1 (ET-1) and endothelin 3 (ET-3) on intramyometrial arteries and myometrial tissue of the uterus from pregnant women at term. Segments of small myometrial arteries (outer diameter 100-500 microns) obtained at cesarean section were isolated and mounted in tissue chambers. The effect of ET-1 and ET-3 on isometric tension was compared with the action of noradrenaline. In similar experiments on myometrial strips, the effect of ET-1 and ET-3 was studied in comparison with oxytocin. ET-1 and ET-3 both produced contractions of arteries and myometrial strips, ET-1 being the most potent. The response of ET-1 was more powerful than the effect of the reference compounds, i.e. noradrenaline with regard to myometrial arteries and oxytocin with regard to the myometrium. It is concluded that endothelins are powerful constrictors of myometrial arteries from pregnant women and possess strong oxytocic effects. In particular, ET-1 could be involved in the regulation of myometrial contractility and/or uteroplacental blood flow.
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PMID:Contractile effects of endothelin 1 and endothelin 3 on myometrium and small intramyometrial arteries of pregnant women at term. 824 91

The intracellular localization of immunoreactive endothelin (ET)-1, and its colocalization with vasopressin (VP) and oxytocin (OT) in the rat neural lobe were investigated by immunogold techniques using specific antisera raised against ET-1, VP, and OT. There were two types of axons: the first contained VP-immunolabeled neurosecretory granules, and the second contained OT-immunolabeled neurosecretory granules. A considerable number of the neurosecretory granules in both types of axon were immunolabeled with antibodies against ET-1, although the VP-immunolabeled granules were more heavily labeled with anti-ET-1 antiserum than OT-immunolabeled ones. Double immunogold labeling clearly demonstrated the intragranular colocalization of immunoreactions for ET-1 and VP and that of immunoreactions for ET-1 and OT. These results suggest that ET in the neural lobe may be released concomitantly with neurohypophysial hormones. Its biological significance remains to be elucidated.
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PMID:Colocalization of immunoreactive endothelin-1 and neurohypophysial hormones in the axons of the neural lobe of the rat pituitary. 842 73

Although it is well known that progesterone alters uterine contractility and plays an important role in maintenance of pregnancy, the biochemical mechanisms by which progesterone alters uterine contractility in human gestation are less clear. In this investigation we sought to identify progesterone-induced adaptations in human myometrial smooth muscle cells that may alter Ca2+ signaling in response to contractile agents. Cells were treated with vehicle or the progesterone analog medroxyprogesterone acetate (MPA) for 5 days, and intracellular free Ca2+ concentration ([Ca2+]i) was quantified after treatment with oxytocin (OX) or endothelin (ET)-1. OX- and ET-1-induced increases in [Ca2+]i were significantly attenuated in cells pretreated with MPA in a dose-dependent manner. Progesterone receptor antagonists prevented the attenuated Ca2+ transients induced by MPA. ETA and ETB receptor subtypes were expressed in myometrial cells, and treatment with MPA resulted in significant downregulation of ETA and ETB receptor binding. MPA did not alter ionomycin-stimulated increases in [Ca2+]i and had no effect on inositol trisphosphate-dependent or -independent release of Ca2+ from internal Ca2+ stores. We conclude that adaptations of Ca2+ homeostasis in myometrial cells during pregnancy may include progesterone-induced modification of receptor-mediated increases in [Ca2+]i.
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PMID:Effect of progesterone on intracellular Ca2+ homeostasis in human myometrial smooth muscle cells. 995 Jul 65

1. Endothelin (ET) and its mRNA are present in endometrium. Expression of ET varies across the menstrual cycle, reaching maximal levels in the premenstrual phase, suggesting a paracrine role in endometrial bleeding and/or repair. 2. The major cellular source of ET is the epithelium, although endothelium and decidualized stroma are additional sites of production. Epithelial ET is the ET-1 isoform and this is able to contract rat thoracic aortic rings ex vivo. 3. Endothelin-1 production by cultured endometrial epithelial cells is markedly increased by serum and, to a lesser extent, by transforming growth factor-beta and interleukin-1 alpha, but not by epidermal growth factor, oxytocin, arginine vasopressin, thrombin or angiotensin II, which stimulate ET production in other tissues. 4. Endothelin-1 has mitogenic actions on endometrial stromal cells; it stimulates the uptake of [3H]-thymidine, acting via the AP-1 cis element c-jun. 5. Neutral endopeptidase (NEP), a membrane-bound ectoenzyme that is capable of degrading ET, is localized principally in endometrial stroma and immunoreactivity is maximal in the secretory phase of the cycle. 6. A potential role for ET in regulating endometrial bleeding is suggested by studies on endometrium from two groups of women who were experiencing abnormal uterine bleeding: users of the contraceptive Norplant (Leiras Co., Turku, Finland) and subjects with documented menorrhagia. In both groups, ET-1 immunoreactivity in endometrial epithelium was markedly reduced compared with the normal menstrual cycle and did not vary cyclically, while NEP immunoreactivity, particularly in the epithelium, was increased. Thus, ET may be involved in endometrial bleeding, as a vasoconstrictor before the onset of menstruation when vasoconstriction is intense and, subsequently, when it may be required in the cessation of menstrual bleeding. Furthermore, the mitogenic actions of ET may play a role in endometrial regeneration and remodelling during the menstrual cycle, particularly following menstruation.
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PMID:Endometrial endothelin: regulator of uterine bleeding and endometrial repair. 1006 38

The precise regulatory mechanisms of cyclic oviductal contraction in the cow are unclear. The purpose of this study was to evaluate the effect of luteinizing hormone (LH), steroids, prostaglandins (PGs) and peptides on the oviductal contraction and secretion of PGs and endothelin (ET-1). In addition, the cyclic expression of mRNA for ET-1 and its receptors (ET-R) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). In the in vitro microdialysis study, an infusion of LH alone or in combination with progesterone (P(4)), estradiol-17beta (E(2)) and/or ET-1 stimulated pronounced release of PGE(2), PGF(2alpha) and ET-1 in the oviducts from cows in the follicular and postovulatory phases. The addition of LH, LH+P(4)+E(2) and/or ET-1 to the medium increased the amplitude of oviductal contraction. However, oxytocin (OT) completely blocked the responses of oviductal secretion and contraction. In contrast, these substances did not show any effect in the oviducts from cows in the mid luteal phase. Similar expression patterns of mRNA encoding for ET-R type A and type B were found, which were highest during the postovulatory phase, lower during the luteal phase, with the lowest expression during the follicular phase. We suggest that the preovulatory LH surge, together with increasing E(2) levels from the Graafian follicle and a basal P(4) from regressing corpora lutea (CL), stimulates maximum oviductal production of PG and ET-1, resulting in oviductal contraction for a rapid transport of gametes. OT released from the newly-formed CL may block these mechanisms, and slow contractions for transport of the embryo to the uterus.
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PMID:In vitro regulation of local secretion and contraction of the bovine oviduct: stimulation by luteinizing hormone, endothelin-1 and prostaglandins, and inhibition by oxytocin. 1113 76


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