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 enzymic inactivation of oxytocin by liver, kidney, uterus and pancreas homogenate subcellular fractions of hens was studied. Oxytocin was most rapidly degraded by the soluble fraction of tissues examined. All the subcellular fractions of liver and kidney inactivated oxytocin, but only the microsomal and soluble fractions of uterus and pancreas showed the oxytocin-inactivating activity. The location of enzymes inactivating oxytocin in subcellular fractions of hen tissues was investigated with the aid of synthetic analogues of oxytocin (deamino-oxytocin and deamino-carba1-oxytocin). The carboxamidopeptidase activity, hydrolyzing the amide bonds in the linear portion of oxytocin was located in the soluble fraction of hen liver, kidney and uterus. No carboxamidopeptidase activity in the pancreatic soluble fraction was found. These results showed that aminopeptidase activity is bound to heavy subcellular particles in the hen tissue. An action of unknown endopeptidases was observed in the microsomal fraction of uterus and pancreas.
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PMID:Inactivation of Oxytocin and its analogues by subcellular fractions of hen tissues. 108 26

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

Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance. Since our previous study showed that placental aminopeptidases degrade vasoactive peptides such as oxytocin, angiotensin and bradykinin, which the fetus actively produces, our present study suggests that the increased vascular resistance in feto-placental circulation in pre-eclampsia is partly controlled by changes in vaso-active peptides, via degradation by placental aminopeptidases.
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PMID:Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia. 151 91

The proteolytic conversion of oxytocin and vasopressin by purified rat brain synaptic membranes 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 synaptic membranes, either C- or N-terminal fragments were found. The most abundant were [Cyt6]oxytocin(4-9), [Cyt6]oxytocin(3-9), [Cyt6]oxytocin(2-9), oxytocin(1-8) and oxytocin(1-7). In contrast, only C-terminal fragments, [Cyt6-Arg8]vasopressin(4-9), [Cyt6-Arg8]vasopressin(3-9) and [Cyt6-Arg8]vasopressin(2-9), were found by incubating [Arg8]vasopressin. The formation of C-terminal oxytocin and vasopressin fragments was inhibited by the aminopeptidase inhibitors amastatin and bestatin, while the formation of oxytocin(1-7) and (1-8) was inhibited by the divalent cations Hg(2+) and Zn(2+). The formation of oxytocin(1-7) was also partially prevented by the endopeptidase inhibitor phosphoramidon. The formation of both C- and N-terminal fragments was inhibited by o-phenanthroline. The results suggest that, while [Arg8]vasopressin is metabolized only by membrane-bound aminopeptidases, oxytocin is also metabolized by membrane-bound endopeptidases.
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PMID:Proteolytic conversion of oxytocin by brain synaptic membranes: role of aminopeptidases and endopeptidases. 180 Sep 50

An aminopeptidase from monkey (Macaca radiata) liver, inactivating oxytocin in vitro and located predominantly in the lysosomal and microsomal fractions, was purified by chromatography on Bio-Gel HTP, DEAE-Sephacel and nickel ion chelate gel and gel filtration on Sephacryl S300. Absence of binding to nickel ion chelate gel indicated the absence of exposed histidine and thiol residues on the enzyme. The enzyme appeared to be a high molecular weight (Mr 106,000) monomeric protein. It was sensitive to inhibition by metal chelators and was found to be a zinc metalloprotein by atomic absorption spectrophotometry. Divalent metal ions Ni2+ and Co2+, and sulphydryl activators glutathione and 2-mercaptoethanol had activating effects, while 4-chloro mercuribenzoate, amino acids with large hydrophobic side chains and L-cystine, beta-lactam antibiotic cloxacillin and peptidase inhibitor amastatin had inhibitory effects on the enzyme activity. The enzyme was most active against S-benzyl L-cysteine 4-nitroanilide substrate. The properties of the enzyme were distinct from those of the well-characterized alanine and leucine aminopeptidases (EC 3.4.11.2 and EC 3.4.11.1 respectively) of liver, and of primate placental cystine aminopeptidases (EC 3.4.11.3).
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PMID:A peptidase activity from primate liver that inactivates oxytocin in vitro: purification and partial characterization. 275 77

Aminopeptidase from dysgerminoma was purified and characterized using L-leucine-beta-naphthylamide as substrate. The enzyme was resistant to puromycin, methionine, amastatin, bastatin, and EDTA, and it was heat labile at 60 degrees C. The enzyme showed the same electrophoretic mobility as pregnant-patient serum oxytocinase CAP1 on polyacrylamide gel electrophoresis. Km value against S-benzylcysteine-p-nitroanilide was 4.2 X 10(-4) M. Oxytocin and vasopressin competitively inhibited the enzyme activity. Molecular weight of the enzyme was estimated to be 80,000 by Sephadex G-200 column chromatography. These results suggest that aminopeptidase from dysgerminoma is an oxytocinase-like enzyme, a placenta-specific protein.
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PMID:Oxytocinase-like enzyme in an ovarian dysgerminoma: a placenta-specific protein. 408 42

1. A thiol proteinase from human pituitaries was purified approximately 400 fold and shown to have different chromatographic properties from that of calf brain. Among substrates cleaved were myelin basic protein, histones, beta-lipotropin, neurophysin, and Substance P. 2. The enzyme showed properties associated with a cathepsin-B like enzyme: dependence on -SH groups, pH optimum of 6.5, inhibition by leupeptin and a synthetic analog, Boc-D-Phe-Pro-arginal, and cleavage of dipeptidyl arylamides with basic residues adjacent to or penultimate to the chromatographic grouping. 3. Membranes present in the P2 fraction of rat brain contained three or more enkephalinases when submitted to DEAE-cellulose chromatography. Further purification on an IgG-Sepharose affinity column prepared with antibody to lung angiotensin converting enzyme indicated the presence of dipeptidyl carboxypeptidase(s) with properties distinct from those of ACE. In addition, the DEAE-cellulose fractions contained various aminopeptidase activities when tested with Leu-Gly-Gly, Leu-Nap, and Ala-Ala-Nap as substrates.
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PMID:Peptide processing in the central nervous system. 625 8

This study concerned the fragmentation of the nonapeptides arginine-vasopressin (AVP-(1-9)) and oxytocin (OXT-(1-9)) by proteolytic enzymes present in a brain synaptic membrane preparation. The peptides formed during digestion of arginine-vasopressin and oxytocin were isolated by high pressure liquid chromatography and chemically characterized by amino acid composition, NH2-terminal amino acid residues, and the presence of 14C radioactivity in tyrosine-2 and glycinamide-9. The major peptide fragments of arginine-vasopressin were [Cyt6]-AVP-(2-9), [Cyt6]-AVP-(3-9), [less than Glu4, Cyt6]-AVP-(4-9), and a peptide having the AVP-(4-8) sequence. The characterized fragments of oxytocin were [Cyt6]-OXT-(2-9), [Cyt6]-OXT-(3-9), [Cyt6]-OXT-(4-9), [less than Glu4, Cyt6]-OXT-(4-9), and [Cyt6] OXT-(5-9). Employing differentially 14C-labeled arginine-vasopressin and oxytocin, the proteolysis of the two peptides into fragments was followed with time. The results showed the sequential formation of peptide fragments by proteolytic cleavage from the NH2 terminus onward, demonstrating the action of an aminopeptidase-like enzyme. Arginine-vasopressin was converted significantly more rapidly by the amino-peptidase activity than oxytocin. In contrast to known brain aminopeptidases, the synaptic membrane-associated activity cleaved the nonapeptides without prior reduction of the disulfide bridge. From the present data it is concluded that aminopeptidases predominate in the proteolytic mechanism by which brain synaptic membranes convert arginine-vasopressin and oxytocin. The role of the proteolytic events and the significance of formed peptide fragments is discussed in view of the concept that arginine-vasopressin and oxytocin are precursors for neuropeptides in brain.
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PMID:Proteolytic conversion of arginine-vasopressin and oxytocin by brain synaptic membranes. Characterization of formed peptides and mechanisms of proteolysis. 633 40

Vasopressin and oxytocin cause behavioral excitation after intracerebroventricular injection in mice. This effect is short-lasting, suggesting that the peptides are rapidly inactivated in the brain. Co-injection of microgram amounts of amastatin, an aminopeptidase inhibitor, prolonged the effect of both vasopressin and oxytocin. Amastatin did not induce large vasopressin-like behavioral effects by itself, nor did it significantly potentiate the action of 1-deamino[1,6-dicarba, 8-arginine] vasopressin (Asu-AVP), an analog that lacks the N-terminal amino group. The effect of Asu-AVP, but not that of vasopressin, was potentiated by phosphoramidon, an inhibitor of neutral metalloendopeptidase ("enkephalinase A"). These results support previous suggestions that vasopressin and oxytocin are inactivated mainly by aminopeptidase action following intracerebroventricular injection.
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PMID:Amastatin potentiates the behavioral effects of vasopressin and oxytocin in mice. 654 Aug 73

In order to elucidate the mechanism of prostaglandin F2 alpha (PGF2 alpha) action to onset of labor, the author observed the changes in maternal peripheral plasma oxytocin, progesterone, estradiol and cystine-aminopeptidase (CAP) activity around the onset of labor by PGF2 alpha. For the investigation, 66 normal pregnant women from 6 to 10 gestational months and same numbers from 39 to 41 gestational weeks were chosen. The blood samples for the latter were drawn just before drip infusion of PGF2 alpha, 5-minutes interval, 3-minutes interval of pain and just after labor. PGF2 alpha administered for labor induction intravenously, and 55 pregnant delivered. 1) The maternal peripheral mean plasma concentrations of them showed increase during pregnancy. There were positive correlations between oxytocin and progesterone, estradiol, CAP. 2) During labor, oxytocin levels increased significantly (p less than 0.01) and progesterone levels decreased significantly (p less than 0.01). On the other hand estradiol levels did not change significantly. CAP levels showed irregular changes. Estradiol-progesterone ratio showed gradual increase. 3) Then during labor, progesterone levels showed negative correlation with oxytocin levels. From this study, the results indicate that significant changes in oxytocin and progesterone and gradual increase estradiol-progesterone ratio are concerned in the onset of labor caused by PGF2 alpha, so labor may progress dynamically.
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PMID:[Changes of oxytocin, progesterone, estradiol and CAP around the labor by prostaglandin F2 alpha (author's transl)]. 694 20


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