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)

Nitric oxide was proposed as an endogenous inhibitor of myometrial contractility during pregnancy. Carbon monoxide (CO) like nitric oxide increases cGMP and is generated during the degradation of heme to biliverdin IX by hemeoxygenases (HO). Here we report that the expression of both HO-1 (inducible) and HO-2 (constitutive) were > 15-fold higher in pregnant myometrium compared to nonpregnant myometrium (n = 4, P < 0.001, P < 0.005, respectively). Moreover, the activation of the HO-CO pathway by the HO inducer, hemin (10 microM), completely inhibited spontaneous contractility (n = 3). Oxytocin-stimulated contractions (n = 5) were also significantly reduced (P < 0.05) in myometrial strips mounted for isometric recording under 2 g tension in Krebs solution. Reverse transcription-PCR analysis revealed that mRNA encoding HO-1 and HO-2 was undetected in explant cultures of nonlaboring pregnant myometrium under basal conditions, however, exposure to progesterone, but not estradiol-17beta, induced the expression of HO-1 and HO-2 mRNAs. Progesterone also significantly induced HO-1 protein synthesis (n = 4, P < 0.001) while estradiol-17beta had no effect (n = 4). In term (37-42-wk gestation) nonlaboring myometrial explants, CO production was stimulated by progesterone (10(-6) M) (n = 2) and hemin (10 microM) (n = 3) after 2 h of incubation and the effect of hemin was inhibited by 1 h of preincubation with the HO inhibitor tin protoporphyrin IX (20 microM). This study clearly demonstrates the expression of HO in the human myometrium and shows that its induction produces CO that limits uterine contractility in pregnant myometrium indicating a role for the HO-CO-cGMP pathway in the maintenance of the quiescent state of the uterus during pregnancy.
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PMID:Hemeoxygenase-1 inhibits human myometrial contractility via carbon monoxide and is upregulated by progesterone during pregnancy. 948 63

This paper discusses the current evidence supporting the notion that endogenous carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally formed in the body during the enzymatic catabolism of heme moieties by heme oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO-3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also possible. Moreover, under pathological conditions, the latter isoform is expressed by activated glial cells. The possible contribution by the recently described HO-3 remains to be established. Once formed, CO exerts its biological effects mainly via the activation of soluble guanylyl cyclase, but alternative signaling mechanisms, such as the activation of cyclooxygenase or the inhibition of cytochrome P450, have also been reported. In in vitro studies, the formation of CO within the hypothalamus has been associated with inhibition of the release of hormones such as corticotropin-releasing hormone, arginine vasopressin and oxytocin involved in hypothalamo-pituitary-adrenal axis activation and, conversely, with stimulation of luteinising hormone-releasing hormone release, thus suggesting that the gas may have a neuroendocrine role which may be to prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and inhibition of reproductive processes within the hypothalamus during stress. At present, however, the possible pathophysiological relevance of the in vitro observations remains to be demonstrated.
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PMID:The role of carbon monoxide in the regulation of neuroendocrine function. 965 Aug 14

Previous in vitro studies have shown that increases in endogenous carbon monoxide (CO) generation via activation of the enzyme heme oxygenase (HO) within the rat hypothalamus are associated with the reduced release of the neuropeptides, vasopressin (AVP) and oxytocin, while evidence concerning corticotrophin-releasing hormone (CRH) is controversial. The present study investigated whether there is also a functional relationship between the HO-CO pathway and AVP and corticosterone (Cort) in vivo. Male Wistar rats were challenged with bacterial lipopolysaccharide (LPS) at doses producing significant activation of the hypothalamo-pituitary-adrenal (HPA) axis. LPS was given alone or after pretreatment with the HO inhibitor Sn-protoporphyrin-9 (SnPP9). The latter was injected either intraperitoneally (i.p.) or by intracerebroventricular (i.c.v.) route. SnPP9 given i.p. failed to modify either basal or LPS-stimulated levels of AVP and Cort. On the contrary, i.c.v. SnPP9 strongly potentiated LPS-induced AVP release and significantly enhanced basal serum Cort levels, although it failed to potentiate stimulation by LPS. The LPS + i.c.v. SnPP9 also significantly reduced the hypothalamic stores of AVP compared to controls, correlating with increased circulating levels of AVP. Taken collectively, these data are in concordance with previous in vitro observations showing that the HO-CO pathway acts centrally to attenuate endotoxin-stimulated AVP release, while having less effects on the pituitary-adrenal axis.
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PMID:Inhibition of heme oxygenase in the central nervous system potentiates endotoxin-induced vasopressin release in the rat. 1050 74

The gaseous neuromodulator carbon monoxide has been shown to reduce the stimulated release of stress neuropeptides, such as vasopressin and oxytocin, from the rat hypothalamus in vitro, while evidence concerning corticotropin-releasing hormone is controversial. In vivo studies have been conducted in the rat, inhibiting heme oxygenase activity--and hence carbon monoxide biosynthesis--in the central nervous system by means of specific heme oxygenase blockers; these studies showed that basal heme oxygenase activity tends to oppose exaggerated increases in vasopressin secretion following immune-inflammatory challenges, whereas it favors the normal rise in circulating ACTH which follows footshock. Another gas normally produced in mammalian brains under basal conditions, hydrogen sulfide, also appears to play a role in the control of the hypothalamo-pituitary-adrenal axis. Indeed, increases in hydrogen sulfide levels within the hypothalamus, either obtained with hydrogen sulfide-enriched media or by the addition of the hydrogen sulfide precursor S-adenosyl-methionine, are associated with the inhibition of the stimulated release of corticotropin-releasing hormone from rat hypothalamic explants. Parellel in vivo experiments in the rat under resting conditions and after stress-induced adrenocortical activation show that S-adenosyl-methionine significantly reduces the rise in serum corticosterone levels caused by 1-h exposure to cold. These results demonstrate the pathophysiological importance of both carbon monoxide and hydrogen sulfide in the regulation of neuroendocrine function.
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PMID:Gaseous neuromodulators in the control of neuroendocrine stress axis. 1126 92

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.
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PMID:L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated pregnant rat uterine strips in vitro. 1132 78

The amount of beta-endorphin-like immunoreactivity (beta-END-LI) in porcine corpora lutea from several stages of the oestrous cycle and the effects of progesterone, oxytocin, and prolactin on beta-END-LI secretion in vitro by luteal cells were studied. Porcine corpora lutea obtained on days 1-5, 6-10, 11-13, 14-18, and 19-21 of the cycle were used to prepare extracts for beta-END-LI determination. Additionally, corpora lutea from days 11-13 and 14-18 were enzymatically dissociated and isolated luteal cells were used for further study of beta-endorphin secretion in vitro. Cells were cultured in serum-free defined M 199 medium (106 cells/ml) at 37 degrees C under 5% CO2 in air, for 12 h. The influences of the following factors on beta-END-LI secretion by luteal cells were tested: progesterone (10-9, 10-7 and 10-5 M), oxytocin (0.01, 0.1, 1 and 10 ng/ml), and prolactin (0.1, 1, 10 and 100 ng/ml). The beta-END-LI contents in extracts and media were measured by radioimmunoassay. The tissue concentration of beta-END-LI was lowest on days 1-5 of the cycle (0.35 +/- 0.03 ng/g wet tissue). Subsequently, it constantly increased to the highest value on days 14-18 (16.58 +/- 0.52 ng/g wet tissue) and on days 19-21 it declined (11.10 +/- 0.52 ng/g wet tissue). Progesterone at a low dose (10-9 M) resulted in significant (p < 0.05) increases and decreases in beta-END-LI secretion by luteal cells from days 11-13 and 14-18, respectively. Higher doses of progesterone (10-7 and 10-5 M) had no effect on beta-END-LI release, compared with the control group. All dose-levels of oxytocin used decreased beta-END-LI secretion by luteal cells on days 11-13 and 14-18 of the cycle. Prolactin at doses of 0.1 and 1 ng/ml on days 11-13, and all doses tested on days 14-18 resulted in decreases in beta-END-LI release from luteal cells. These results document evident changes in beta-END-LI content in the pig corpus luteum during its development and indicate the potential roles of progesterone, oxytocin, and prolactin in luteal cell secretion of beta-END-LI.
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PMID:The content of beta-endorphin-like immunoreactivity in porcine corpus luteum and the potential roles of progesterone, oxytocin and prolactin in the regulation of beta-endorphin release from luteal cells in vitro. 1132 64

Erythromycin has a well-known dual effect on the contractility of the gastrointestinal system and recently has also been shown to inhibit contractions of the rat myometrium. The aim of the present study was to investigate the effects of clarithromycin on oxytocin, prostaglandin F2alpha (PGF2alpha) and KCl-induced contractions of human myometrium in vitro. Myometrial strips were obtained from pregnant women undergoing elective Cesarean section and the strips were suspended in a jacketed organ bath filled with Krebs solution at 37 degrees C (pH 7.4) and continuously aired with 95% oxygen and 5% carbon dioxide. Isometric contractions were measured using a force displacement transducer. Oxytocin, PGF2alpha, KCl and clarithromycin were applied to the tissue bath and the amplitude and frequency of contractions were evaluated at 20-min intervals. Freidmann analysis of variance, Kruskal Wallis and Wilcoxon Rank tests were used for statistical analysis of the data. Clarithromycin dose dependently inhibited the amplitude of contractions independent of the stimulus. Pre-treatment with apamin prevented clarithromycin-induced effects on amplitude and frequency of contractions. We conclude that the macrolide antibiotic clarithromycin may have a direct inhibitory effect on contractions of human myometrium.
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PMID:Clarithromycin inhibits myometrial contractions in isolated human myometrium independent of stimulus. 1223 15

The aim of the present study was to evaluate the possible direct effects of GnRH, oxytocin (OT) and vasoactive intestinal peptide (VIP) on the release of LH and PRL by dispersed porcine anterior pituitary cells. Pituitary glands were obtained from mature gilts, which were ovariectomized (OVX) one month before slaughter. Gilts randomly assigned to one of the four groups were treated: in Group 1 (n = 8) with 1 ml/100 kg b.w. corn oil (placebo); in Group 2 (n = 8) and Group 3 (n = 8) with estradiol benzoate (EB) at the dose 2.5 mg/100 kg b.w., respectively, 30-36 h and 60-66 h before slaughter; and in Group 4 (n = 9) with progesterone (P4) at the dose 120 mg/ 100 kg b.w. for five consecutive days before slaughter. In gilts of Group 2 and Group 3 treatments with EB have induced the negative and positive feedback in LH secretion, respectively. Isolated anterior pituitary cells (10(6)/well) were cultured in McCoy's 5a medium with horse serum and fetal calf serum for 3 days at 37 degrees C under the atmosphere of 95% air and 5% CO2. Subsequently, the culture plates were rinsed with fresh McCoy's 5A medium and the cells were incubated for 3.5 h at 37 degrees C in the same medium containing one of the following agents: GnRH (100 ng/ml), OT (10-1000 nM) or VIP (1-100 nM). The addition of GnRH to cultured pituitary cells resulted in marked increases in LH release (p < 0.001) in all experimental groups. In the presence of OT and VIP we noted significant increases (p < 0.001) in LH secretion by pituitary cells derived from gilts representing the positive feedback phase (Group 3). In contrast, OT and VIP were without any effect on LH release in Group 1 (placebo) and Group 2 (the negative feedback). Pituitary cells obtained from OVX gilts primed with P4 produced significantly higher amounts (p < 0.001) of LH only after an addition of 100 nM OT. Neuropeptide GnRH did not affect PRL secretion by pituitary cells obtained from gilts of all experimental groups. Oxytocin also failed to alter PRL secretion in Group 1 and Group 2. However, pituitary cells from animals primed with EB 60-66 h before slaughter and P4 produced markedly increased amounts of PRL in the presence of OT. Neuropeptide VIP stimulated PRL release from pituitary cells of OVX gilts primed with EB (Groups 2 and 3) or P4. In contrast, in OVX gilts primed with placebo, VIP was without any effect on PRL secretion. In conclusion, the results of our in vitro studies confirmed the stimulatory effect of GnRH on LH secretion by porcine pituitary cells and also suggest a participation of OT and VIP in modulation of LH and PRL secretion at the pituitary level in a way dependent on hormonal status of animals.
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PMID:The influences of GnRH, oxytocin and vasoactive intestinal peptide on LH and PRL secretion by porcine pituitary cells in vitro. 1236 40

This study was designed to elucidate the effects of meluadrine tartrate on oxytocin-induced uterine contraction and maternal hemodynamics in unanesthetized, chronically instrumented pregnant goats. After the administration of meluadrine tartrate or ritodrine hydrochloride to pregnant goats, changes in heart rate (HR), arterial blood pressure (AOP), and arterial blood pH and gasses (P(O2) and P(CO2)) in the mother, as well as changes in intrauterine pressure (IUP) and uterine arterial blood flow (UBF), were measured. The escalating administration of meluadrine tartrate (0.03, 0.1, 0.3 and 1 micro g. kg(-)(1). min(-)(1)) or ritodrine hydrochloride (1, 3, 10 and 30 microg. kg(-)(1). min(-)(1)) to the maternal femoral vein caused a marked and similar inhibition in oxytocin-induced uterine contraction (a rise in IUP). By these escalating dosings, maternal HR was increased dose-dependently in both treatment groups; however, the degree of the HR increase in the meluadrine tartrate-treatment group was significantly less than that in the ritodrine hydrochloride-treatment group. Furthermore, the degree of the UBF decrease in the meluadrine tartrate-treatment group was significantly less than that in the ritodrine hydrochloride-treatment group. The present study suggests that meluadrine tartrate has a mild influence on the maternal cardiovascular function relative to the effects of ritodrine taking the potent efficacy on oxytocin-induced uterine contraction into account.
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PMID:Effects of meluadrine tartrate and ritodrine hydrochloride on oxytocin-induced uterine contraction, uterine arterial blood flow and maternal cardiovascular function in pregnant goats. 1241 79

The objective of this study was to establish an experimental model for extracorporeal perfusion of swine uterus. In order to validate this model, we examined some biochemical parameters and determined the effect of oxytocic drugs (Oxytoxin, Prostaglandin E (2)) on extracorporeal perfused swine uteri. Thirty swine uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer for a period up to eleven hours with the aim to preserve a viable organ, which should be responsive to hormones. The intrauterine pressure was recorded after administration of various concentrations of oxytocin and prostaglandin E (2). Perfusate pH, perfusate lactate, partial oxygen and carbon dioxide tensions, oxygen saturation, and hydrogencarbonate levels in the perfusate, all indicators of tissue ischemia or cell necrosis, showed good preservation of the organ for up to seven hours. We examined the relation of intrauterine pressure to oxytocin and prostaglandin E (2). Both were able to induce contractions of the uterus, whereas prostaglandin E (2) produced rhythmical contractions of smaller amplitude and a higher frequency. We could demonstrate that our perfusion system was able to preserve the swine uterus in a functional condition appropriate for the study of physiological questions.
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PMID:The extracorporeal perfusion of swine uterus as an experimental model: the effect of oxytocic drugs. 1451 66


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