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)

The effects of cyanide and nitrogen on contractile activity in rat uteri was investigated. Hypoxia significantly reduced contractile activity produced either spontaneously, or by application of carbachol (50 mumol l-1) or oxytocin (20 nmol l-1) in preparations from pregnant and nonpregnant rats. Hypoxia had, however, significantly smaller effects on agonist-evoked than on spontaneous contractions. Application of agonists under hypoxic conditions restored some degree of force to preparations in which spontaneous activity had been abolished. This result suggests that the loss of spontaneous contractions was, in part, due to decreased excitability of the uterus, rather than to an impairment of the contractile machinery. Hypoxia significantly decreased the force produced by depolarization of the uterus. The effects of hypoxia on contraction produced by agonists or depolarization were not significantly different, suggesting that a similar mechanism may maintain force under these conditions, and that this mechanism does not occur during spontaneous activity. Lowering the external Ca2+ concentration to 0.1 mmol l-1 resulted in production of significantly less force in the presence or absence of agonist. The ability of hypoxia to decrease agonist-induced force was found not to be due to the intracellular acidification it produces. It was concluded that uterine hypoxia may decrease uterine contractions in vivo and a possible role in dystocia during labour was discussed.
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PMID:Effects of hypoxia on force produced by agonists and depolarization and arising spontaneously in the rat uterus. 810 37

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.
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PMID:Effect of chronic hypoxia on myometrial responsiveness in the pregnant rat. 863 96

To determine if there are inter-relationships between progesterone, oxytocin (OT), dopamine (DA), noradrenaline (NA) and ascorbic acid, these compounds were measured in the corpus luteum (CL) from cattle at different stages of the oestrous cycle (n = 42) and from 1-5 months of pregnancy (n = 27). They were measured by radioimmunoassay (RIA), high performance liquid chromatography (HPLC) and colorimetric methods. Corpora lutea were collected from heifers and cows within 30 min of slaughter on days 1-5, 6-10, 11-16 and 17-21 of the oestrous cycle. The stage of pregnancy was determined on the basis of foetal size and development. Each CL was divided into four parts and stored in liquid nitrogen. For hormone estimation, the tissue was homogenised/powdered and suspended in phosphate buffer (for OT and progesterone), 0.1 M trichloracetic acid (TCA; for catecholamines) or in ice-cold metaphosphoric acid (for ascorbic acid). There were no significant differences in the measured parameters between cows and heifers, and so the data were combined. The concentration of DA was correlated with NA (r = 0.66; P < 0.001) during the oestrous cycle and was highest in newly formed CL (P < 0.01) as compared with early CL, regressed CL and CL of pregnant females. NA was negatively correlated (P < 0.01) with progesterone (r = -0.53) and OT (r = -0.41). In contrast, progesterone and OT were positively correlated with each other (r = 0.81; P < 0.01) during all stages of the oestrous cycle, but not during pregnancy. The lowest concentrations of ascorbic acid were observed in regressed CL. Ascorbic acid concentrations were correlated (P < 0.01) with those of progesterone (r = 0.68), OT (r = 0.42) and DA (r = -0.37). Luteal concentrations of ascorbic acid, progesterone and OT followed a pattern consistent with the development and regression of the CL. Luteal concentrations of catecholamines were not consistent with this pattern.
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PMID:Concentrations of catecholamines, ascorbic acid, progesterone and oxytocin in the corpora lutea of cyclic and pregnant cattle. 1049 56

A series of 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides structurally related to diazoxide and pinacidil were synthesized and tested as possible K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. In contrast to previously described 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1, 1-dioxides, most of the new compounds were found to be poorly active on B-cells but exhibited clear vasorelaxant properties. 3-(3, 3-Dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (4d) and 7-chloro-3-(3, 3-dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (5d), two compounds bearing the alkyl side chain of pinacidil, were found to be the most active representatives of their respective series on rat aorta rings. 3-Cycloalkylalkylamino- and 3-aralkylamino-7-chloro-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides also expressed myorelaxant activity on electrically stimulated guinea pig ileum and on oxytocin-induced contractions of the rat uterus. Further biological investigations ((86)Rb efflux measurements, vasodilator potency on 30 and 80 mM KCl-induced contractions in the absence and presence of glibenclamide) revealed that compounds 4d and 5d, but not compound 5f, expressed the pharmacological profile of classical K(ATP) channel openers. In conclusion, by changing the position of the nitrogen atom in the pyridine ring, we now have obtained a family of drugs expressing an opposite tissue selectivity. Taken as a whole, the present findings also suggest that 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides such as 4c, 4d, 5c, and 5d may be considered as new examples of K(ATP) channel openers expressing a pharmacological profile similar to that of pinacidil and diazoxide.
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PMID:3-Alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil as potassium channel openers acting on vascular smooth muscle cells: design, synthesis, and pharmacological evaluation. 1078 Sep 1

The secretory peptides luteinizing hormone-releasing hormone, enkephalin, angiotensin, and oxytocin are biochemical antioxidants in aqueous medium. These hormones scavenge free peroxyl radicals, prevent the oxidation of low-density lipoprotein, and inhibit lipid peroxidation in brain membranes. Their capacity to directly suppress free radical-mediated reactions is demonstrated by electron-spin resonance spectroscopy. Electrospray ionization-mass spectrometry analysis of the free radical-quenching reaction reveals distinct oxidation products, including peptide dimers. Moreover, secretory peptide hormones can scavenge reactive nitrogen species derived from nitric oxide and peroxynitrite. An analysis of the structure-activity relationship indicates that their antioxidant activity is derived from the occurrence of solvent-exposed tyrosine and tryptophan residues, which is consistent with the mass spectrometry results. Significant effects in vitro can be observed at nanomolar concentrations, which makes these peptides comparable in potency with classic antioxidants having low molecular mass. Secretory peptide hormones may constitute an important part of the antioxidant defense system, and the sequences of the described antioxidant peptides may be unique lead structures for the rational design of novel antioxidant drugs having an improved pharmacological profile.
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PMID:Secretory peptide hormones are biochemical antioxidants: structure-activity relationship. 1180 49

The primary objective was to determine whether the dietary polyunsaturated fatty acids, eicosapentaenoic (EPA, C20:5, n-3) and docosahexaenoic (DHA, C22:6, n-3), present in fish meal (FM) can attenuate uterine secretion of PGF2alpha in response to a challenge with estradiol and oxytocin in lactating dairy cows. Cycling multiparous cows (n = 32) were fed diets containing 0 (OFM), 2.6 (2.6FM), 5.2 (5.2FM), or 7.8% menhaden FM (7.8FM). The diet consisting of 7.8FM also contained fish oil (0.28% of dietary dry matter) to increase intake of EPA and DHA. Average dry matter intake was 24.9 kg/d and unaffected by diet. Combined intakes of EPA and DHA averaged 0, 12.8, 24.1, and 54.0 g/d from the OFM, 2.6FM, 5.2FM, and 7.8FM diets, respectively. At 30 to 34 d after initiation of dietary treatments, cows received an i.m. injection of 100 microg of GnRH followed by i.m. administration of 25 and 15 mg of PGF2alpha after 7 and 8 d, respectively. Synchronous ovulation was induced by an injection of 3000 IU of human chorionic gonadotropin (hCG) given 24 h later on d 9. Subsequent luteal phase increases in plasma progesterone concentrations did not differ (0.88 ng/ml per day). At 15 d after hCG injection, cows were injected with estradiol-17beta (3 mg, i.v.) at 0900 h and oxytocin (100 IU, i.v.) at 1300 h. Plasma PGF2alpha metabolite concentrations after oxytocin injection were reduced in cows fed diets containing FM compared with those fed OFM. Milk production (39.1 kg/d) and concentrations of fat, protein, or urea nitrogen in milk were not affected by diet. Feeding fish meal and fish oil containing eicosapentaenoic acid and docosahexaenoic acid reduced the proportion of n-6 fatty acids and increased that of n-3 fatty acids in milk in a dose-responsive manner.
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PMID:Uterine, ovarian, and production responses of lactating dairy cows to increasing dietary concentrations of menhaden fish meal. 1201 20

Previous studies have suggested that upstream stimulatory factors (USFs) regulate genes involved with cell cycle progression. Because of the relationship of USFs to an important oncogene in breast cancer, c-myc, we chose to determine the importance of USF to normal mammary gland development in the mouse. Expression of USF in the mammary gland throughout development demonstrated only modest changes. Mutation of the Usf2 gene was associated with reduced fertility in females, but had no effect on prepartum mammary gland development. However, lactation performance in Usf2-/- females was only half of that observed in Usf2+/+ females, and both lactose and nitrogen were decreased in milk from Usf2-/- dams. This decrease was associated with diminished mammary tissue wet weight and luminal area by d 9 of lactation and with a decreased protein-DNA ratio. This decrease was associated with reduced abundance of the eukaryotic initiation factors eIF4E and eIF4G. Blood oxytocin concentrations on d 9 postpartum were also lower in Usf2-/- mice than Usf2+/+ mice. In contrast, the mutation had no effect on blood prolactin concentrations, mammary cell proliferation or apoptosis, mammary tissue oxytocin receptors, or milk protein gene expression. The mutation had only modest effects on maternal behavior. These data support the idea that USF is important to physiological processes necessary for the establishment and maintenance of normal lactation and suggest that USF-2 may impact lactation through both systemic and mammary cell-specific mechanisms.
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PMID:Diminished milk synthesis in upstream stimulatory factor 2 null mice is associated with decreased circulating oxytocin and decreased mammary gland expression of eukaryotic initiation factors 4E and 4G. 1290 52

Pittman, K. A. (Agricultural Research Service, Beltsville, Md.), and M. P. Bryant. Peptides and other nitrogen sources for growth of Bacteroides ruminicola. J. Bacteriol. 88:401-410. 1964.-Representative strains of Bacteroides ruminicola were found to utilize peptide nitrogen or ammonia nitrogen, but not to utilize significant amounts of free amino acid nitrogen or the nitrogen from a variety of other low molecular weight compounds for growth. All strains grew well in a defined medium containing glucose, minerals, B-vitamins, heme, volatile fatty acids, methionine, and cysteine, with ammonia as the main nitrogen source. Methionine and cysteine were required by some strains. The only compounds found to replace ammonia as the main nitrogen source were a few proteins; tryptic digests of protein; peptide-rich fractions of Sephadex G-25 fractionated tryptic digests of casein; and the octapeptides, oxytocin and vasopressin. Most of the nitrogen present in these compounds was utilized. However, the organism did not utilize nitrogen from any of 12 dipeptides, triglycylglycine, glutathione, or mixtures of free amino acids. Possible reasons for the inability of B. ruminicola to utilize low molecular weight nitrogen compounds are discussed.
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PMID:PEPTIDES AND OTHER NITROGEN SOURCES FOR GROWTH OF BACTEROIDES RUMINICOLA. 1420 57

The availability of human tissue for experimental purposes is often problematical and use is thus made of animal tissue as models of the human tissue. In this study, porcine vaginal mucosa was used as an in vitro permeability model for human vaginal mucosa using tritium-labelled permeants (17beta-estradiol, r-arecoline, vasopressin, oxytocin and water). Fresh porcine and human vaginal tissues were frozen in liquid nitrogen and stored at -85 degrees C. In vitro permeability studies were performed using a flow-through diffusion apparatus (24 h, 20 degrees C, 1.5 ml/h). The mean steady state flux values for water, r-arecoline and vasopressin were approximately 4, 12 and 5% lower, while those for 17beta-estradiol and oxytocin were approximately 17 and 53% higher, through porcine vaginal mucosa as compared to human vaginal mucosa, respectively. Using a F-test (comparing whole curves), statistically significant differences in the diffusion of 17beta-estradiol, r-arecoline and oxytocin were indicated when comparing human and porcine vaginal mucosa. Generally, porcine vaginal mucosa seems a good in vitro permeability model for human vaginal mucosa. However, permeability of these two mucosa towards all permeants tested does not always correspond closely. These differences must always be considered when using porcine tissue as an in vitro permeability model for human vaginal mucosa.
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PMID:Porcine vaginal mucosa as an in vitro permeability model for human vaginal mucosa. 1622 13

The interaction of the cyclic nonapeptide oxytocin (OT) with a number of alkaline earth and divalent transition metal ions (X(2+)) was examined employing mass spectrometry (MS) and ion mobility spectrometry (IMS) techniques in combination with molecular dynamics (MD) and density functional theory (DFT) calculations. Under acidic conditions it was found that OT exhibits an exceptionally strong affinity for all divalent metal ions resulting in strong [OT + X](2+) peaks in the mass spectrum. Under basic conditions only Cu(2+) and Ni(2+)-OT complexes were detected and these were singly, doubly, triply, or quadruply deprotonated. Collision-induced dissociation of the [OT - 3H + Cu](-) complex yielded exclusively C-terminal Cu(2+)-containing fragments (Cu(2+)fragment(3-)), suggesting that the Cu(2+) ligation site includes deprotonated C-terminal backbone amide nitrogen atoms and the N-terminal amino nitrogen atom in [OT - 3H + Cu](-). MD and DFT calculations indicate a square-planar complex is consistent with these observations and with experimental collision cross sections. MD and DFT calculations also indicate either an octahedral or trigonal-bipyramidal complex between Zn(2+) and OT is lowest in energy with carbonyl oxygens being the primary ligation sites. Both complexes yield cross sections in agreement with experiment. The biological impact of the structural changes induced in OT by divalent metal ion coodination is discussed.
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PMID:Interactions of the hormone oxytocin with divalent metal ions. 1839 1


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