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)

Two different forms of oxytocinase (L-cystine aminopeptidase, CAP; EC 3.4.11.3) were purified from the 9000 g and 105000 g precipitate fractions of human placenta homogenate by sequential chromatography on columns of hydroxyapatite, DE-32, nickel ion affinity, and Sephadex G-200. One species (CAP-I) purifed from the mitochondrial/lysosomal fraction migrated on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis with an apparent molecular mass of 61 kDa; the other (CAP-II) from the microsomal fraction was composed of two subunits with molecular masses of 56 and 40 kDa. The molecular masses of CAP-I and CAP-II estimated by gel filtration were 64 and 97 kDa, respectively. The specific activities of the two species for S-benzyl-L-cysteine p-nitroanilide increased by 357- (for CAP-I) and 139-fold (for CAP-II) compared with the starting preparations. The optimal pH values toward the artificial substrate were approx. 7.4-8.0 for CAP-I and 6.8-8.0 for CAP-II. The Km and Vmax values toward oxytocin were 5.6 microM and 23.4 micromol/h/mg protein for CAP-I, and 38 microM and 15.6 micromol/h/mg protein for CAP-II. Both enzymes were inhibited by the metal-chelating agents, EDTA and o-phenanthroline, whereas they were specifically activated by addition of Co2+: CAP-I was more sensitive to these reagents than CAP-II. L-Methionine strongly inhibited CAP-I, while CAP-II activity was only slightly affected. CAP-II was more sensitive to amastatin than CAP-I. Thus, the two enzymes are quite distinct in their molecular nature and biochemical properties. They may play a regulatory role in the metabolism of oxytocin and other biologically active peptides in intact placenta.
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PMID:Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization. 901

Both oxytocin (OT) and [Arg8]vasopressin (AVP) are found within the ovine pineal gland and may function to modulate melatonin secretion. However, the receptors which mediate the actions of these peptides have yet to be characterised. Preliminary studies of ovine pineal microsomal cell membranes showed binding of [3H]OT (79+/-9 fmol/mg) 10 times greater than binding of [3H]AVP (8+/-3 fmol/mg). Saturation studies using either [3H]OT or the selective OT receptor ligand [125I]d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin (OTA) revealed high affinity, single site kinetics (Kd = 1.72+/-0.32 nM; Bmax = 68+/-18 fmol/mg). Binding of [3H]AVP was more effectively displaced by OT than AVP, suggesting that binding may be due to cross-reaction with the OT binding site. Displacement of [3H]OT using a range of selective agonists and antagonist analogues revealed pharmacological characteristics similar to [3H]OT binding sites in the ovine and rat uterus. These data show that the ovine pineal expresses a high density of OT binding sites which may participate in the regulation of melatonin secretion.
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PMID:Pharmacological characterisation of oxytocin binding sites in the ovine pineal gland. 925 May 78

Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.
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PMID:Metabolism of oxytocin in rat uterus and placenta in late gestation. 931 84

To develop a novel delivery system for peptides involving sugar modification, Arg-vasopressin (AVP) was modified by linking it to a variety of sugars via an octamethylene group and the subsequent tissue uptake by rats was then monitored after administration by i.v. injection. The glucosyl, mannosyl, and 2-deoxyglucosyl derivatives of AVP exhibited selective renal uptake. These derivatives were found to be distributed in the proximal tubules of the renal cortex. In addition, they exhibited specific binding to the kidney microsomal fraction in vitro (Kd = approximately 60 nM), suggesting that they are taken up by a specific recognition mechanism located in the kidneys. From the results of the uptake study of glucosyl derivatives, the following points are clear: 1) renal uptake in vivo becomes saturated with increasing dose, and the Km from the uptake study is almost the same as the Kd obtained in the binding assay in vitro and 2) because the renal first-pass uptake extraction is about 70% at a low dose (10 nmol/kg), there is an effective mechanism for uptake from blood. Furthermore, glucosyl and mannosyl derivatives of oxytocin, a neutral peptide, unlike AVP that is basic, also have high renal uptake clearances. Thus, the renal uptake may not be dependent on derivatives having a cationic nature. We conclude that there is a novel transport mechanism in the kidneys that can be used for the specific renal delivery of glycosylated peptides.
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PMID:Specific renal delivery of sugar-modified low-molecular-weight peptides. 991 3

The induction of endometrial prostaglandin (PG) F2alpha synthesis by oxytocin is dependent upon activation of phospholipase (PL) A2 and mobilization of arachidonic acid. The objective of this study was to determine if oxytocin stimulates PGF2alpha synthesis by inducing synthesis of cytosolic PLA2 (cPLA2). In Experiment 1, 15 ovariectomized ewes were given progesterone and estradiol to simulate an estrous cycle. Ewes were then given an injection of oxytocin on Day 14 of the simulated estrous cycle. Jugular blood samples were collected and assayed for 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Uteri were collected at 0, 7.5, 25, 90, or 240 min postinjection (n = 3 ewes/time point). Total RNA was isolated from caruncular endometrium and subjected to dot-blot analysis. Oxytocin induced a rapid and transient increase in serum PGFM (P < 0.01). However, endometrial concentrations of cPLA2 mRNA did not change following oxytocin administration (P > 0.10). In Experiment 2, 11 ovary-intact ewes were given oxytocin (n = 5) or saline (n = 6) on Day 15 after estrus. Jugular blood samples were collected and assayed for serum concentrations of PGFM. Uteri were collected at 15 min postinjection. Homogenates were prepared from caruncular endometrium and subjected to Western blot analysis. Concentrations of PGFM were higher in oxytocin treated ewes compared to saline treated ewes at 15 min postinjection (P < 0.01). Endometrial concentrations of cPLA2 protein were greater in the cytosolic than in the microsomal fraction (P < 0.01). Oxytocin did not affect the amount of cPLA2 protein in either fraction (P > 0.10). In conclusion, oxytocin did not effect expression of either cPLA2 mRNA or protein in ovine endometrium. Oxytocin may stimulate PGF2alpha synthesis by activating cPLA2 protein that is already present in an inactive form.
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PMID:Effect of oxytocin on expression of cytosolic phospholipase A2 mRNA and protein in ovine endometrial tissue in vivo. 1111 88

Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial. Furthermore, possible changes in its traffic under metabolic challenges are unknown. The present study investigated the catalytic activity attributable to EC 3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and reproducibility of subcellular adipocyte fractionation procedure were demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde traffic and aminoacyl preference occurred independently of insulin stimulation. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin.
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PMID:Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity. 2599 80


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