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)

Fetal membranes were obtained in connection with 1st-trimester abortion and vaginal delivery or elective caesarean section at term. Pieces of the isolated amnion membrane were incubated in vitro with [3H]proline or [3H]glucosamine in the presence of prostaglandin (PG) E2 or oxytocin. PGE2 reduced the labelling with [3H]proline in the 1st trimester and in membranes obtained at vaginal delivery, whereas an increase of incorporation was observed before start of labour. Oxytocin reduced [3H]proline labelling at any stage. In membranes from vaginally delivered women both oxytocin and PGE2 stimulated the incorporation of [3H]glucosamine, whereas oxytocin diminished radiolabelling in the other experimental groups. Regarding the radiolabelling with [3H]proline and [3H]glucosamine as reflecting the de novo formation of collagen and proteoglycans, respectively, it is suggested that both PGE2 and oxytocin, by their influence on connective tissue metabolism, may regulate the tensile properties of the fetal membranes.
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PMID:The influence of prostaglandin E2 and oxytocin on the incorporation of [3H]proline and [3H]glucosamine in the human amnion. 399 20

The effect of oxytocin on collagen synthesis in the pregnant human cervix and lower uterine segment was studied in incubation experiments by measuring the incorporation of 3H-proline. Oxytocin had a concentration related inhibitory effect on the labelling with 3H-proline. Vasopressin in the corresponding concentrations had only a weak effect on the incorporation of 3H-proline. Addition of indomethacin did not influence the response to oxytocin indicating that the effect was probably not mediated by prostaglandins. These results suggest that oxytocin under in vitro experimental conditions influences cervical connective tissue metabolism which is in contrast to current clinical experience.
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PMID:Oxytocin and cervical connective tissue. 401 69

Uptake of individual amino acids and peptides by Fusiformis necrophorus was studied in growing cultures and resting cell suspensions. The cells were able to incorporate 16 of 17 (14)C-labeled amino acids into cell protein, the exception being proline. Proline could neither be formed by the cells from any of the other tested amino acids nor be synthesized from glucose or serine when these were used as energy sources. The addition of di- and tripeptides, the octapeptides vasopressin and oxytocin, and the poly (24) peptide ACTH did not stimulate cell growth, but a marked stimulatory effect was noted after the addition of poly-l-proline (mean molecular weight 2,000). It is concluded that cells of F. necrophorus (i) possess transport systems for most amino acids but not for proline, (ii) are dependent on exogenous proline in the form of proline-containing peptides for growth, and (iii) may be cultivated in a defined amino acid medium provided the proline requirement is met by the addition of a proline-containing peptide.
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PMID:Amino acid and peptide requirement of Fusiformis necrophorus. 474 17

A conformation of the neurohypophyseal hormone oxytocin in solution is proposed. The structure possesses, in addition to the beta-turn comprised of the sequence -L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl- in the ring component of the hormonal molecule, a second beta-turn involving the C-terminal oxytocin sequence, -L-cysteinyl-L-prolyl-L-leucylglycinamide. The resulting oxytocin structure places the bulky side chains of the leucine and isoleucine residues, as well as the cyclic moiety of the proline residue, at corners of the two beta-turns. A critical role is played by the asparagine residue: its peptide N-H participates in the formation of the hydrogen-bonded cyclic structure of the beta-turn in the ring component of oxytocin and its peptide C=O can be hydrogen-bonded to the N-H of tyrosine, while its side chain C=O stabilizes the second beta-turn by forming a hydrogen bond with the N-H of the leucine residue, which is part of the end peptide of the second beta-turn. This conformational assignment of oxytocin is consistent with hydrogen-deuterium exchange studies, with plots of temperature dependence of peptide proton chemical shifts, and with the coupling constants for the NH-CH dihedral angles.
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PMID:Proposed conformation of oxytocin in solution. 528 May 29

Eight analogues of oxytocin and arginine-vasopressin were synthesized, in which the proline residue in position 7 was replaced by either sarcosine or N-methylalanine; some of the pharmacological properties of these analogues were evaluated. In peptides containing a beta-mercaptopropionic acid residue in position 1, the additivity of the effects of deletion of the amino group in position 1 and of the above-noted replacements in position 7 on biological properties of these analogues was ascertained. All of the analogues were found to be potent in either antidiuretic or uterine activity and also selective in action. From the point of view of pharmacological properties, substitution of sarcosine in position 7 of oxytocin gave analogues with higher oxytocic and milk-ejecting activities than did the substitution of N-methylalanine. The opposite structure-activity relationship was observed with arginine-vasopressin, where the N-methylalanine-containing analogues were more potent than the sarcosine-containing analogues with respect to pressor activity and also, if not deaminated, with respect to antidiuretic activity.
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PMID:Synthesis and some pharmacological properties of oxytocin and vasopressin analogues with sarcosine or N-methyl-L-alanine in position 7. 618 21

A post-proline cleaving enzyme and its endogenous inhibitor have been demonstrated to be present in sperm of the ascidian, Halocynthia roretzi. The enzyme was extracted with artificial sea water from frozen and thawed sperm and isolated from accompanying acrosin-like and chymotrypsin-like enzymes by DEAE-cellulose chromatography. It was then separated from the endogenous inhibitor by ammonium sulfate fractionation and DEAE-Sephacel chromatography. Three subsequent chromatographic operations using hydroxylapatite, Sephadex G-150 and Z-Gly-Pro-Leu-Gly-aminohexyl-Sepharose yielded the highly purified enzyme. The molecular weight and isoelectric point of the enzyme were estimated to be 66,000 and 5.5, respectively. The pH optimum of the activity was 7.0. The enzyme was inactivated with diisopropylphosphorofluoridate, phenylmethylsulfonyl fluoride, Z-Gly-Pro-chloromethyl ketone and sulfhydryl-directed reagents; these inhibitor susceptibilities were similar to those reported for the enzymes of mammalian origins. The ascidian enzyme hydrolyzed oxytocin, angiotensin II, luteinizing hormone releasing hormone and neurotensin at the carboxyl side of proline residues. The endogenous inhibitor was heat stable. The molecular weight of its main component was estimated to be about 8,000. The presence of salt at high concentrations weakened the enzyme-inhibitor interaction. Z-Gly-Pro-chloromethyl ketone inhibited fertilization of the ascidian, suggesting possible involvement of the post-proline cleaving enzyme in fertilization.
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PMID:Isolation and characterization of a post-proline cleaving enzyme and its inhibitor from sperm of the ascidian, Halocynthia roretzi. 636 Oct 7

The effect of oxytocin on collagen metabolism in the cervix and lower uterine segment of pregnant women was studied by measuring the incorporation of [3H]proline in vitro. Oxytocin had a concentration related inhibitory effect on the labelling with [3H]proline. Addition of indomethacin did not influence the response to oxytocin indicating that the effect was not directly mediated by prostaglandins. Oestradiol-17 beta potentiated the effect of oxytocin. Vasopressin decreased the incorporation of [3H]proline slightly but the action of this hormone was significantly less than that of oxytocin. The results suggest that oxytocin under in vitro experimental conditions influences cervical connective tissue metabolism which is in contrast to current clinical experiences.
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PMID:Effects of oxytocin on cervical and uterine connective tissue. 673 Aug 60

A bovine brain thyrotropin-releasing-factor (thyroliberin) deamidase has been purified 1100-fold to apparent homogeneity. Molecular weight estimates by gel filtration and sodium dodecylsulfate gel electrophoresis indicate that the enzyme consists of a single polypeptide chain of molecular weight of about 62 000-65 000. The enzyme is inactivated by sulfhydryl blocking agents. Serine proteinase inhibitors, phenylmethanesulfonyl fluoride and benzamidine, have no effect. Besides thyroliberin, the enzyme hydrolyzes peptide bonds involving the carboxyl group of proline residues in luliberin, tuftsin, angiotensin II, melanotropin, and neurotensin. Oxytocin, vasopressin, and bradykinin are not cleaved; they are, however, strong competitive inhibitors of thyroliberin deamidation. The specificity studies indicate that the enzyme is a "post-proline cleaving enzyme" which hydrolyzes peptides of the general structure, Yaa-Pro-Xaa, in which Xaa = amino acid, peptide, or amide (not Pro), and Yaa = N-blocked basic amino acid or a peptide sequence in which the C-terminal residue (i.e. the residue prior to Pro) is a basic amino acid such as His, Lys, or Arg. The enzyme is compared to other post-proline cleaving enzymes.
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PMID:Purification and properties of a bovine brain thyrotropin-releasing-factor deamidase. A post-proline cleaving enzyme of limited specificity. 679 65

A post-proline cleaving enzyme [post-proline endopeptidase: EC 3.4.21.26] was purified from lamb brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and Sephadex G-150. The purified enzyme appeared homogeneous on disc gel and sodium dodecyl sulfate (SDS) gel electrophoreses. The enzyme was most active at pH 7.0 with carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap) as a substrate and catalyzed the hydrolysis of oxytocin, vasopressin, thyrotropin releasing hormone (TRH), substance P, luteinizing hormone releasing hormone (LH-RH), and angiotensin at the carboxyl side of their proline residues, except for the Pro2-Lys3 bond in substance P. From the results of subsite mapping using synthetic peptides, five subsites, S3 to S2', for substrate interaction with the enzyme were deduced to be present, and high stereospecificity was observed at S2, S1, and S1'. The isoelectric point of the enzyme was at pH 4.9, and the molecular weights estimated by gel filtration and SDS gel electrophoresis were 74,000 and 77,000, respectively. The enzyme was markedly inhibited by diisopropylphosphoro fluoridate (DFP), carbobenzoxy-Gly-Pro-chloromethyl ketone (Z-Gly-Pro-CH2Cl), p-chloromercuribenzoate (PCMB), Hg2+, and Cu2+ ions. These enzymatic and protein chemical properties of post-proline cleaving enzyme from lamb brain closely resemble those of the lamb kidney enzyme, except for the molecular weight. In the present work, however, we decided that the molecular weight of the enzyme from lamb kidney was also 74,000, which is different from that reported previously (J. Biol. Chem. 251, 7593 (1976) but is in accord with the value of post-proline cleaving enzyme from lamb brain.
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PMID:Post-proline cleaving enzyme from lamb brain. 702 30

Substitution of the amino acid glycine for 7-proline in oxytocin produces an analog, [7-glycine]oxygocin, having markedly reduced antidiuretic and vasopressor activities but retaining considerable natriuretic activity. We administered this analog alone and with distally acting diuretic agents to test the hypothesis that oxytocin and its analogs decrease proximal tubular fluid reabsorption. If [7-glycine]oxytocin shares a common mechanism of action with any of these agents, the response to combined treatment should be less than additive, otherwise, the saluretic effect of both agents should be maintained. Subcutaneous administration of [7-glycine]oxytocin, 10 micrograms/kg, to conscious fluid-loaded rats produced a natriuresis, diuresis and kaliuresis. Hydrochlorothiazide and [7-glycine]oxytocin administered together to the same rats had a greater than additive effect on urine volume and sodium excretion. Furosemide and [7-glycine]oxytocin had an additive effect on urine volume, sodium and chloride excretion. Triamterene blocked the kaliuresis caused by [7-glycine]oxytocin, although the two agents administered together had a greater than additive effect on sodium excretion. These results indicate that [7-glycine]oxytocin does not share a common natriuretic mechanism or site of action with the above diuretics. Our data are consistent with the hypothesis that oxytocin and its analogs may increase urinary sodium excretion by decreasing net proximal tubular fluid reabsorption.
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PMID:Natriuretic effect of [7-glycine]oxytocin in the presence of diuretic agents in conscious rats. 735 43


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