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 responses of isolated frog skin to 5-hydroxytryptamine (increased active sodium transport and decreased passive chloride permeability) are diminished by incubation with the enzymes neuraminidase and N-acetylneuraminic acid aldolase but only in the absence of Ca2+ and presence of EDTA. The responses induced by oxytocin, adrenalin and aldosterone are unaffected by enzyme treatment.
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PMID:Selective destruction of 5-hydroxytryptamine receptors by neuraminidase. 31 8

1. Two enzymes acting on the linear portion of oxytocin: carboxamidopeptidase (releasing Gly . NH2) and prolyl peptidase (releasing Leu-Gly . NH2) were identified in the cytoplasmic fraction of chicken liver. 2. Carboxamidopeptidase was purified 134-fold with a 23% yield, and prolyl peptiase 71-fold with a 20% yield. The specific activity of the final preparations was 181 and 96 microU/mg protein, respectively. 3. The optimum pH for carboxamidopeptidase was 6.0--6.5 and for prolyl peptidase, 7.5. Carboxamidopeptidase activity was inhibited by Mn2+, Zn2+, Ca2+, Co2+, and stimulated by EDTA; the activity of prolyl peptidase was inhibited by Zn2+ and Mn2+. The Km value of both enzymes for oxytocin was 1.5--2.4 microM.
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PMID:Partial purification and characterization of the oxytocin-inactivating enzymes from chicken liver. 39 2

The reaction products of plasma enzyme degradation of TRH were identified by thin layer chromatography. The enzyme in normal rat plasma yields proline and pGlu-His as major reaction products. High concentrations of proline decrease peptide cleavage, resulting in greater amounts of acid TRH. The apparent Km of the enzyme is 4.1 X 10(-6) M. LHRH and neurotensin are competitive inhibitors with Ki of 5 X 10(-6) M and 1.5 X 10(-5) M, respectively. Somatostatin, MIF, oxytocin, arg-vasopressin, arg-vasotocin, neurophysin II and glucagon do not compete; and pGlu-His-Pro-OH, Glu-His-Pro-OH, pGlu-His, His-Pro-NH2, and Pro-NH2 do not affect enzyme activity. These data suggest that the substrated requires pGlu and a terminal or internal amide to complex with the enzyme. The enzyme is markedly inhibited by Cu++, Bal, benzamadine, p-(chloromercuri)-benzoic acid, moderately affected by EDTA and puromycin, and unaffected by mercaptoethanol. TSH does not affect enzyme activity while LH inhibits it moderately at high concentrations (300-600 pg/ml).
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PMID:Characteristics of the plasma TRH-degrading enzyme. 81 19

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

The proteolytic conversion of oxytocin and Arg8-vasopressin by purified rat thymocytes was studied at 37 degrees C and physiological pH 7.4. The formed peptide fragments were isolated by high performance liquid chromatography and characterized by amino acid analysis. When oxytocin was incubated with rat thymocytes, oxytocin 1-8 and oxytocin 1-7 were isolated. In contrast, only Arg8-vasopressin 1-8 was found when Arg8-vasopressin was incubated with thymocytes. The formation of oxytocin 1-8, oxytocin 1-7 and Arg8-vasopressin 1-8 was prevented partially by 10(-3) M phenylmethylsulfonyl fluoride and iodoacetamide, and abolished by 0.5 x 10(-3) M Zn2+ and Hg2+ ions and 10(-3) M o-phenanthroline, but not by 10(-5) M leupeptin, lima bean trypsin inhibitor, trasylol, captopril and phosphoramidon. 0.5 x 10(-3) M EDTA was without effect on the formation of oxytocin 1-8 and Arg8-vasopressin 1-8 but increased by about 30% the formation of oxytocin 1-7. The results suggest that proteases capable of metabolizing oxytocin and Arg8-vasopressin are localized in the thymocyte surface membrane. Since oxytocin and vasopressin are synthetized by thymic epithelial cells and exert several actions on thymocytes, these proteases may play a physiological role in the inactivation of neurohypophyseal peptides at the thymocyte level.
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PMID:Proteolytic conversion of neurohypophyseal peptides by rat thymocytes: involvement of endopeptidases. 164 Oct 73

We previously reported that prolactin (PRL) could increase the activity of ornithine decarboxylase (ODC) in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). This action of the hormone was inhibited by oxytocin (OT), the calcium ionophore A23187, and diacyglycerol (DG) and was duplicated by 10 microM verapamil (VML), a calcium channel blocker. Here, we expand these results to show that 1) a higher dose of VML (50 microM) produces an additive effect with PRL; 2) addition of small amounts of calcium (0.1 mM) to the liver culture medium blocks PRL action; 3) neither nifedipine (NIF), a different type of calcium channel blocker, nor EDTA alter PRL action; and 4) gossypol, a reported inhibitor of protein kinase C, mimics PRL action. Additionally, we show that PRL increases ODC activity in tiger salamander tail skin in vitro, a tissue previously demonstrated to be a PRL target tissue in this species. The same set of treatments which we have shown to modify PRL effects on ODC in liver slices affects PRL action in the tail skin in a parallel manner. Thus, the mechanism whereby PRL enhances ODC activity appears to be the same in both these tissues. These results are discussed in conjunction with the findings from similar studies using mammalian tissues in an attempt to assess the current picture of the mechanism of PRL action and the possible role of inositol phospholipid turnover, calcium, and protein kinase C in the action of this hormone.
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PMID:Reduced calcium and inhibition of protein kinase C mimic the enhancement of ornithine decarboxylase activity of prolactin in Ambystoma tigrinum tissues. 194 Aug 22

The effect of four eicosanoid synthesis inhibitors (ESIs): mepacrine (6 x 10(-6) to 10(-4) M), nordihydroguaiaretic acid (NDHGA, 10(-6) to 10(-5) M), indomethacin (2 x 10(-6) and 2 x 10(-5) M) and imidazole (10(-5) and 10(-4) M), were studied on contractions induced by cumulative doses (4 and 20 mU/ml) of oxytocin (OT) on the uterus of rats both in natural estrus and ovariectomized. ESIs were also assayed on contractions induced by carbachol (10(-4) M) and KCl (60 mM) in rat uterus under natural estrus, and OT (10 mU/ml)-induced contractions in rat uterus incubated in calcium-free EDTA treated medium. Mepacrine, NDHGA and indomethacin, but not imidazol, inhibited in a dose-dependent way contractions induced by OT in the uterus. The effect was higher in ovariectomized than in natural estrus rats. Mepacrine and NDHGA, but not indomethacin or imidazole, inhibited contractions induced by carbachol and relaxed tonic contractions to KCl (60 mM). Mepacrine, NDHG and indomethacin also inhibited tonic contractions by OT in calcium-free EDTA treated medium. Our results suggest that mepacrine, NDHGA and indomethacin, independently of inhibition of eicosanoids synthesis, reduce the entry of extracellular calcium and/or the release of intracellular calcium.
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PMID:Effects of some inhibitors of arachidonic acid metabolism in rat uterus in vitro. 205 42

The presence of the human placental enzyme, oxytocinase, in blood samples taken during pregnancy causes major methological problems in the radioimmunoassay for plasma oxytocin. Inadequate inhibition of the enzyme activity may lead to spuriously high or low values of plasma oxytocin. This study systematically investigates a variety of enzyme inhibitors. The optimum inhibitory system was obtained by the addition of 10 microliters of cold 125 mmol/l 1.10 phenanthrolene and 1 mol/l EDTA per ml of whole blood into the syringe. Complete enzyme inhibition was maintained for up to 60 min, during which time the lithium heparinized plasma samples were extracted by the Florisil method. Following extraction there was no enzyme activity in the extract residue. Concentrations of phenanthrolene and EDTA necessary to eliminate enzyme activity were 50- and 10-fold greater, respectively, than in any previously reported method. Recovery of synthetic oxytocin added to pregnancy plasma with inhibitors was 80% or higher, over the concentration range 1-100 pmol/l. Extract residue could be stored at -20 degrees C for up to 7 weeks. Dilutions of pregnancy plasma extracts ran parallel to the oxytocin standard curve. Studies on plasma concentrations of oxytocin (OT) during the first stage of labour in 6 patients showed that 3 had pulsatile plasma OT, peak values ranging from 4-10 pmol/l in phase with uterine concentrations, but 2 who had regular uterine activity had no episodic changes in plasma OT. One patient with hypocontractile labour had low non-fluctuating plasma OT.
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PMID:Evaluation of enzyme inhibitors of pregnancy associated oxytocinase: application to the measurement of plasma immunoreactive oxytocin during human labour. 243 27

The effects of MgCl2 on the oestrogen-dominated rat uterus have been examined. Tissues were preincubated in a Ca2+- and Mg2+-free medium containing 3 mM EDTA. Most experiments were subsequently performed in a similar medium containing either no EDTA or EDTA (1 mM). When MgCl2 was added cumulatively (1-32 mM) no contractile responses were obtained in Ca,Mg-free medium or in Ca,Mg-free high K+ solution. When 2 mM CaCl2 was added, a sustained contraction was obtained. Subsequent addition of cumulative concentrations of MgCl2 caused concentration-dependent relaxation. Oxytocin, 2 microM, produced a small and sustained contraction in a Ca,Mg-free medium. Addition of MgCl2, 2 mM, increased this contraction. In a Ca,Mg-free medium vanadate (8 X 10(-5)M) did not evoke spasm of uterine smooth muscle. After addition of MgCl2 in cumulative amounts (1-32 mM) in the presence of vanadate, a concentration-dependent contraction was obtained. The present work shows that in Ca-free solution, maintained contractions induced by oxytocin and vanadate are augmented by Mg2+.
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PMID:Effects of magnesium chloride on the contractile response of uterus to several agonists in Ca-free solution. 288 1

A comparison was made of contractions produced by submaximal doses of oxytocin, noradrenaline, PGE2 and PGF2 alpha in estrogen-dominated rat uterus after the preparation had been loaded in Ca-free medium supplemented with EDTA 3 mM. The experiments were carried out in the presence of EDTA 1 mM to complex the contaminating Ca. The contraction was sustained as long as the preparation was exposed to the drug and was relaxed by washing. Cumulative concentration-response curves to oxytocin (6.25-100 microM), noradrenaline (0.05-1.6 mM), PGE2 (0.1-1.6 microM) and PGF2 alpha (0.02-0.32 microM) were made. The threshold concentration for PGF2 alpha was much lower than for PGE2, oxytocin and noradrenaline. Isoprenaline (10- -10(-4)M), KCl (56.3 mM) and caffeine (5 mM) were added. The results showed that isoprenaline and KCl did not produce contractile response. Caffeine produces only a small decrease in the resting tension and this effect is not reversible. After addition of noradrenaline, a concentration of oxytocin (6 microM) produced a uterine contraction smaller than the control response of uterus to oxytocin. The response to the oxytocin applied after washing out the caffeine was the same as the control response. All agonists tested that were capable of inducing uterine contraction in Ca-free medium act through specific receptors. This suggests a relation between receptor-operated Ca-channels and intracellular Ca-stores.
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PMID:Role of intracellular calcium stores in the contractile response of uterus to several agonists. 310 89


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