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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dissociation course of the hormone receptor complexes of rat myometrial oxytocin receptors was studied. The dissociation course was biphasic with a major component displaying an almost irreversible binding character (time constant 0.003 min-1). This irreversibility was independent of hormonal status of the myometrium as well as the type of divalent cation present in the medium, and was not caused by endocytosis of the receptor. However, as addition of EDTA caused an immediate dissociation of all receptor binding, the irreversibility must be of a non-covalent character. It is suggested that new analysis methods for receptor kinetics including the possibility of partly irreversible binding mechanisms should be considered.
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PMID:The nature of receptor binding of oxytocin in myometrial tissue. 838 57

The release of the nonapeptides oxytocin and vasopressin within the hypothalamic supraoptic and paraventricular nuclei was measured in 30-min microdialysates in conscious female rats in the last three days of pregnancy, during parturition, immediately after parturition and during suckling, all in the same rats, and in virgin controls. Nonapeptide release within the supraoptic and paraventricular nuclei was unchanged during late pregnancy compared to virgin rats, but intranuclear oxytocin and not vasopressin release was elevated during parturition (relative to late pregnancy, supraoptic nucleus: to 254%, paraventricular nucleus: to 300%; P < 0.01) and during suckling also on days 8-10 of lactation (relative to pre-suckling, supraoptic nucleus: to 407%, paraventricular nucleus: to 275%; P < 0.02). Suckling-induced release of oxytocin was significantly reduced using Ca(2+)-free, EDTA-containing (10(-4) M) microdialysis fluid and further stimulated by high K(+)- (56 mM), veratridine-containing (50 microM) microdialysis fluid. The opioid antagonist naloxone whether given by subcutaneous injection (5 mg/kg) or directly into the supraoptic nucleus by microdialysis (5 x 10(-6) M) or microinjection (1.5 microliters, 10(-6) M) did not further enhance oxytocin release within either the supraoptic or paraventricular nuclei during parturition. In contrast to the selective release of oxytocin within the supraoptic and paraventricular nuclei during parturition and suckling, direct osmotic stimulation of the nuclei by microdialysing hypertonic medium (artificial cerebrospinal fluid; 1 M NaCl) increased intranuclear release of both oxytocin and vasopressin which was further enhanced after replacement of hypertonic with isotonic fluid. This rebound phenomenon served to confirm the precise location of the microdialysis probe ante mortem and the ability of the nuclei to adequately respond to the osmotic stimulus at the end of the experiment. The study has shown that oxytocin is released in the supraoptic and paraventricular nuclei during parturition as well as in lactation unrestrained by endogenous opioids during parturition. This intranuclear release of oxytocin may act by local positive feedback stimulation of oxytocin neurons to excite further oxytocin release in the brain and into blood during both parturition and lactation.
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PMID:Oxytocin and vasopressin release within the supraoptic and paraventricular nuclei of pregnant, parturient and lactating rats: a microdialysis study. 846 13

1. The effects of estrogens estradiol (E2, 10(-6)-10(-4) M) and diethylstilbestrol (DES, 10(-6)-10(-4) M) and the antiestrogens nafoxidine (N, 10(-6)-10(-4) M), tamoxifen (T, 10(-6)-6 x 10(-4) M), tamoxifen ethyl bromide (TEB, 10(-4) M) and ICI 164,384 (ICI, 10(-5) M) on tonic contractions induced by oxytocin (2 x 10(-8) M) or vanadate (3 x 10(-4) M) in rat uterus incubated in calcium-free EDTA treated solution have been assayed. 2. E2 and DES relaxed the tonic contraction induced by oxytocin in a dose dependent way (EC50: 1.11 +/- 0.01 x 10(-4) M and 1.5 +/- 0.07 x 10(-5) M). The vanadate-induced contraction only was relaxed with DES (57.62 +/- 2.38% at 10(-3) M). 3. The effect of DES on oxytocin contraction was unmodified by the protein synthesis inhibitor cycloheximide (10 micrograms/ml) and by the cyclooxygenase inhibitor indomethacin (3 x 10(-6) M), but enhanced by the intracellular calcium release inhibitor TMB-8 (10(-5) M). The antiestrogen tamoxifen (3 x 10(-5) M) promotes the relaxing effect of DES. 4. The antiestrogens N, and T, but not ICI, relaxed the oxytocin-induced contraction (EC50: 4.51 +/- 0.43 x 10(-5) M and 2.27 +/- 0.05 x 10(-4) M). TEB (10(-4) M) produces a relaxation of 74.5 +/- 2.11%. The vanadate contraction is also relaxed by T (EC50: 6.03 +/- 0.04 x 10(-4) M). 5. The effect of T on oxytocin contraction was unmodified with cycloheximide or TMB-8 but decreased with indomethacin.
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PMID:Estrogen and antiestrogen non-genomic effect in rat uterus contraction in calcium-free solution. 848 24

Parquetina nigrescens (Afz.) Bullock (Periplocaceae) hydromethanolic extract (PAR) in reference solution exerts a stimulating and spasmogenic action on the pregnant rat myometrium in vitro. This action is characterised by increasing amplitude of spontaneous isometric contractions and a slight elevation of muscular basic tonus. These effects on myometrium may be compared with those provoked by sulprostone (PGE2) in the same experimental conditions. In calcium free solution, Parquetina nigrescens extract could restore partially spontaneous contractile activity. On the contrary, in presence of EDTA PAR induces a complete abolition of the activity. On the other hand, in calcium free solution, sulprostone is able to develop a clear elevation of basic tonus (contracture). These observations support the hypothesis that the extract has an oxytocin-like effect, which is characterised by an extracellular influx of calcium, responsible for the increase of the maximum isometric contraction amplitude. Sulprostone activates both extracellular and intracellular calcium responsible for the increase of contractile activity and development of the contracture of uterine smooth muscle.
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PMID:Uterotonic effects of hydromethanolic extract of Parquetina nigrescens (Periplocaceae) on spontaneous contractile activity in the isolated myometrium of pregnant rats. 880 72

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

The intestinal absorption enhancement of the nonapeptide [Mpa1,D-Arg8]vasopressin (dDAVP) by medium-chain glyceride vehicles was studied using an in vivo rat model. Rats were gavaged with dDAVP formulated with three different lipid vehicles: (1) monohexanoin, (2) mixed monoglycerides, diglycerides and triglycerides of hexanoic acid and (3) monoglycerides, diglycerides and triglycerides of octanoic and decanoic acids, and with saline as control. The marker absorption into blood and urine was followed for 24 hr. All lipid vehicles enhanced the oral bioavailability of dDAVP, but monohexanoin gave the highest increase, approximately 10 times that of control. In contrast to dDAVP, the stable and more lipophilic nonapeptide analog [Mpa1,D-Tyr(ethyl)2,Val4,D-Arg8]oxytocin did not show increased urine recovery when formulated with monohexanoin. A 2-fold increase in urine recovery of the inert low-molecular-weight marker [51Cr]EDTA was observed when formulated with monohexanoin. With use of the fluorescent marker Evans blue formulated with monohexanoin, an elevated accumulation of Evans blue in the mucus layer was observed after incubation in in situ loops. No mucosal damage after lipid vehicle gavage was observed by light microscopic evaluation. Medium-chain glycerides functioned well as oral absorption enhancers of the model peptide dDAVP, and monohexanoin showed the highest enhancement capacity. The mechanisms of this enhancement appear to be related to a protection against luminal dDAVP degradation, mucoadhesive properties of the vehicle and, possibly, an altered epithelial absorption pathway.
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PMID:Enhancing effects of monohexanoin and two other medium-chain glyceride vehicles on intestinal absorption of desmopressin (dDAVP). 926 18

The signal pathway for bradykinin-induced contraction of the uterine smooth muscle was investigated by comparing the effect of blocking agents on bradykinin and oxytocin induced contractions of the isolated rat uterus in organ bath. The phospholipase C inhibitor U-73,122 abolished the effect of both bradykinin and oxytocin. Inhibition of non-voltage-dependent Ca2+ influx by SK & F 96,365 reduced the contraction induced by both agonists to about 20% of control. The tissues failed to contract when they were exposed to bradykinin or oxytocin in Ca(2+)-free Krebs-Henseleit buffer with 2 mM EDTA. Both bradykinin and oxytocin induced further contraction when the tissues were partially depolarized and partially contracted by 30 mM KCl. These observations suggest that bradykinin, like oxytocin, activates phospholipase C which generates IP3 with a subsequent release of Ca2+ from intracellular stores followed by store-operated Ca2+ influx. Thus, membrane potential independent steps appear to be important in bradykinin-induced contraction in the rat uterus.
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PMID:Bradykinin causes contraction in rat uterus through the same signal pathway as oxytocin. 977 24

A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 microM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With M(r) 85 kDa the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 microM) and for atrial natriuretic peptide (Km = 5 microM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.
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PMID:A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide. 1034 68

Human leptin expressed by E. coli had been used to treat human obesity in American and scientists had achieved good effects, the researchers here wanted to know whether human leptin can be expressed in the mammary glands of transgenic animas. In this study, human leptin gene about 1.0 kb, the terminator of rabbit whey acid protein gene (rWAP) about 0.2 kb and the promoter including the distal upstream region and part of the first exon of rWAP gene about 6.3 kb were used to construct a expression vector. Before we did the subclonings, the sequences of the human leptin gene were sequenced by ABI377 DNA Sequencer, the results showed that the fragment of human leptin gene included the last nine base pairs of the first exon, the complete sequences of the second exon(172 bp) and parts of the third exon(including part of the encoding sequences and part of the 3' untranslated region). The final expression vector was digested with NotI and a fragment of 7.5 kb was collected and dissolved in TE(10 mmol/L Tris.Cl, pH7.4; 0.1 mmol/L EDTA) for later microinjection. The concentration of DNA was about 2 micrograms/mL, the copy number in 1 mL was about 2.4 x 10(11), every 1 to 2 pL of the prepared DNA solution was microinjected into the mouse embryos at pronucleus stage. After standard microinjection procedures, 48 live mice were obtained. The tails of the mice were cut(about 0.1 g) at four weeks of age, genomic DNA was extracted and digested completely with EcoRI, two were confirmed to be transgenic mice(both were female) by Southern hybridization using DIG labeled human leptin gene as probe, transgenic rate among the mice born was about 4% (2/48). The two female transgenic mice(2# and C3) were mated with nontransgenic male mice. The two founder transgenic mice were segregated with their baby mice for at least three hours at the fifth day after parturition and were milked by intraperitoneal injection of 0.3 IU of oxytocin and udder massage. SDS-PAGE was used to analyze whether there were expression of human leptin in the milk of the two founder transgenic mice with the milk of non-transgenic mouse at fifth day after parturition as control. SDS-PAGE results showed that compared with the control there was a new band in both of the founder transgenic mice milk, and its molecular weight was about 16 kD, which was quite similar with that of the human leptin. The researchers estimated that the expression level of this protein in the milk of the transgenic mice was about 1-2 mg/mL.
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PMID:[A study on the expression of human leptin in the mammary glands of transgenic mice]. 1133 Jan 96

The properties of recombinant Aeromonas punctata prolyl endopeptidase(apPEP) were studied using specific substrate and peptides. Results show that the optimum catalytic temperature and pH was 34 degrees and 8.4, the stability of the apPEP was in the range of 4-32 degrees and pH 6.0-10.0, and its K(m) was 0.03 mmol/L based on the Z-Gly-Pro-betaNA. The apPEP was not sensitive to PMSF, TLCK, TPCK, Trypsion inhibitor, EDTA, tetrathionate and some metal ions, but was sensitive to SDS and Zn(2 ), and was completely inhibited by DFP. Oxytocin and calcitonin could be specifically hydrolyzed by apPEP at the carboxyl site of proline residue, but the hydrolysis efficiency of calcitonin by the enzyme was less than for oxytocin and for Z-Gly-Pro-betaNA.
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PMID:Properties of Recombinant Aeromonas punctata Prolyl Endopeptidase. 1211 Sep 36


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