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 endopeptidase, post-proline cleaving enzyme, has been purified 10,500-fold in an overall yield of 18% from lamb kidney. The enzyme possesses a specific activity of 45 mumol/mg/min as tested with the substrate Z-Gly-Pro-Leu-Gly (Km = 6.0 X 10(-5)), has a molecular weight of 115,000, is comprised of two subunits with a molecular weight of 57,000, and exhibits maximal activity at pH 7.5 to 8.0. With the exception of the -Pro-Pro linkage, the -Pro-X-peptide bond (X equals L- and D-amino acid residues) located internally in the peptide sequence can be hydrolyzed (cleavage occurs faster when X = lipophilic side chain as compared to X = acidic side chain). The appropriate -Pro-X- bonds in zinc-free porcine insulin, oxytocin, arginine vasopressin, angiotensin II, bradykinin-potentiating factor were cleaved. Human gastrin, adrenocorticotropic hormone, denatured guinea pig skin collagen, and ascaris cuticle collagen were not degraded. Dipeptides with the structure Z-Pro-LD-X competitively inhibit post-proline cleaving enzyme.
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PMID:Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography. 1 73

Platelet function has been studied during intravenous, intraamniotic, and extraamniotic administration of prostaglandin F2alpha (PgF2alpha) for termination of missed abortion and missed labor, for therapeutic abortion, and for induction of term labor. The controls received oxytocin i.v. (missed labor and term labor). Our investigations have shown that there was a normalization of the increased spontaneous platelet aggregation and a significant reduction of ADP- and collagen-induced platelet aggregation in the groups given PgF2alpha i.v. The desaggregation in these groups was increased. The other groups given PgF2alpha showed no significant changes in platelet function. Inducing labor by oxytocin we found a tendency to increased platelet aggregation and decreased desaggregation. The clinical importance of these findings and the consequences for hemostasis are discussed.
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PMID:Studies on platelet function during different modes of administration of PgF2alpha in obstetrics and gynecology. 58 Oct 52

We discovered an enzyme in human platelets that deamidates substance P and other tachykinins. Because an amidated carboxyl terminus is important for biological activity, we purified and characterized this deamidase. The enzyme, released from human platelets by thrombin, was purified to homogeneity by ammonium sulfate precipitation, followed by chromatography on an octyl-Sepharose column and chromatofocusing on PBE 94. The purified enzyme exhibits esterase, peptidase, and deamidase activities. The peptidase activity (with furylacryloyl-Phe-Phe) is optimal at pH 5.0 while the esterase (benzoyl-tyrosine ethyl ester) and deamidase (D-Ala2-Leu5-enkephalinamide) activities are optimal at pH 7.0. With biologically important peptides, the enzyme acts both as a deamidase (substance P, neurokinin A, and eledoisin) and a carboxy-peptidase (with bradykinin, angiotensin I, substance P-free acid, oxytocin-free acid) at neutrality, although the carboxypeptidase action is faster at pH 5.5. Enkephalins, released upon deamidation of enkephalinamides, were not cleaved. Gly9-NH2 of oxytocin was released without deamidation. Peptides with a penultimate Arg residue were not hydrolyzed. Some properties of the deamidase are similar to those reported for cathepsin A. The deamidase is inhibited by diisopropylfluorophosphate, inhibitors of chymotrypsin-type enzymes, and mercury compounds while other inhibitors of catheptic enzymes, trypsin-like enzymes, and metalloproteases were ineffective. In gel filtration, the native enzyme has an Mr = 94,000 while in non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis the Mr = 52,000 indicating it exists as a dimer. After reduction, deamidase dissociates into two chains of Mr = 33,000 and 21,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. [3H]diisopropylfluorophosphate labeled the active site serine in the Mr = 33,000 chain. The first 25 amino acids of both chains were sequenced. They are identical with the sequences of the two chains of lysosomal "protective protein" which, in turn, has sequence similarity to the KEX1 gene product and carboxypeptidase Y of yeast. This protective protein complexes with beta-galactosidase and neuraminidase in lysosomes and is vitally important in maintaining their activity and stability. A defect in this protein is the cause of galactosialidosis, a severe genetic disorder. The ability of physiological stimuli (e.g. thrombin or collagen) to release the deamidase from platelets indicates that it may also be involved in the local metabolism of bioactive peptides.
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PMID:A peptidase in human platelets that deamidates tachykinins. Probable identity with the lysosomal "protective protein". 169 76

Bovine granulosa cells were cultured in collagen (Vitrogen 100)-pretreated wells using defined medium to study the secretion of oxytocin and progesterone under serum-free conditions. Secretion of oxytocin began spontaneously after the first day and was maintained at a high level during a 1 week culture period. Addition of serum to the medium reduced oxytocin concentrations by up to 90%. There were positive exponential relationships between oxytocin and progesterone concentrations and the inoculated cell density (range, 1.67 to 23.4 X 10(5) cells/ml/well). The results indicate that neither serum nor gonadotrophins are required for in vitro differentiation of bovine granulosa cells and that addition of serum may attenuate subsequent hormone secretion. This culture system should provide a better in vitro model for the study of ovarian oxytocin secretion than those previously described.
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PMID:Greatly elevated and sustained secretion of oxytocin by bovine granulosa cells in serum-free culture. 276 9

Tissue pieces from the wall (i.e. tunica albuginea with adjacent theca externa) of human follicles were incubated with and without various hormones and their potential influence upon the collagenolytic activity was evaluated. Following incubation the collagenase activity was determined in the incubation medium by measurement of the hydrolytic activity against the synthetic peptide 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH. Stimulated collagenolytic activity was seen in the presence of relaxin and oxytocin whereas prostaglandin E2, prostaglandin F2 alpha, progesterone and 17 beta-estradiol were without effect. It is concluded that the stimulated collagenolytic activity induced by relaxin and oxytocin may be of importance for the degradation of collagen which occurs prior to follicular rupture.
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PMID:Hormonal effects on collagenolytic activity in the isolated human ovarian follicular wall. 301 21

Oxytocin immunoreactivity was determined in follicular fluid from human follicles at different stages of development. The concentration of oxytocin was highest in pre-ovulatory follicles. The measured oxytocin was found to co-elute with synthetic oxytocin in an h.p.l.c. system. The influence of oxytocin on the incorporation of [3H]proline into isolated human follicular wall was studied in vitro. Oxytocin induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles, indicating an inhibitory effect on collagen synthesis. This effect of oxytocin was not affected by indomethacin. An oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin, did not inhibit the incorporation of [3H]proline. The pre-ovulatory augmentation of oxytocin concentration in follicular fluid might reflect a physiological role for oxytocin in the ovulatory process. This assumption is strengthened by the observation that oxytocin may influence follicular collagen metabolism in vitro and by this means participate in the regulation of follicular rupture in the human.
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PMID:Oxytocin in human follicular fluid and its possible role in the ovulatory process as studied in vitro. 355 70

Dams with 7 pups each were randomly assigned to two different diets. Twelve dams were fed a normal (20%) protein diet and were divided into two groups of 4 and 8 animals. Pups from group 1 (n = 28) were injected with citrate buffer as a control. Pups from group 2 (n = 56) were injected with streptozotocin. Twelve additional dams were fed a 40% protein diet. They were also divided into two groups of 4 and 8 animals. Pups from group 3 (n = 28) were injected with citrate buffer as a control. Pups from group 4 (n = 56) were injected with streptozotocin. Forty-eight hours later, diabetic status was determined using Dextrostix. On Day 15, pups were injected with [14C]proline to determine collagen synthesis and 45Ca to study mineralization. After the pups were killed, blood glucose levels were determined. Then mandibles were removed. Milk from each dam was also collected after injection of oxytocin. At the time of killing, blood glucose levels in diabetic pups were less than earlier levels, though still higher than those of controls on either diet. The weights of body and mandible, collagen contents, and the total calcium contents in the diabetic group were in general less than those of the nondiabetic group on the 20 and 40% protein diets. 45Ca uptake in the diabetic group was significantly increased compared with those of the nondiabetic rats on both diets. The percentage reduction in the mandibles of diabetic rats from those of nondiabetic rats on the 40% protein diets was consistently less than that of animals on the 20% protein diets. The higher protein contents of the maternal milk in the 40% protein group may partly be responsible for the smaller impairment of mandibular development in the diabetic over nondiabetic animals. It is concluded that maternal low-carbohydrate high-protein diets will play indirectly a beneficial role in the development of the mandibles of diabetic newborns.
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PMID:Maternal low-carbohydrate high-protein diet affects mandibular growth in diabetic newborn rats. 357 31

Pieces of intact or degenerated sciatic nerves autografted into contact with transected neurosecretory axons within the hypothalamus were invaded by neurophysin-positive axons. With increasing time after grafting, increasing numbers of axons were present in both types of grafts, but grafts of degenerated sciatic nerves always contained more axons. At the fine-structural level typical neurosecretory as well as nonneurosecretory axons were usually associated with basal lamina-enclosed neurolemmocyte processes; occasional axons occurred among collagen fibrils or within basal lamina scaffolds. Profiles with the fine structural characteristics of axon terminals were present by 20 days after transplantation.
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PMID:Peptidergic neurosecretory axons regenerate into sciatic nerve autografts in the rat hypothalamus. 380 16

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


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