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

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.
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PMID:Neonatal stress transiently alters the development of hippocampal oxytocin receptors. 795 35

Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not.
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PMID:Estrogen increases affinity of oxytocin receptors in the medial preoptic area-anterior hypothalamus. 799 51

In this study oxytocin (OT) receptors have been characterized and localized in the testis of the rat using the radioiodinated OT receptor antagonist 125I-labelled d(CH2)5 [Tyr(Me)2,Thr4,Tyr9-NH2]-vasotocin (OTA). Receptor density and localization have been compared with the rat testis arginine vasopressin (AVP) receptor using the radioiodinated AVP V1a receptor antagonist 125I-labelled d(CH2)5Sar7-AVP and the radioiodinated linear AVP V1a antagonist 125I-labelled [(C6H5-CH2CO)-O-methyl-D-Tyr-Phe-Gln-Asn-Arg-Pro- Arg-Pro-Arg-Tyr-NH2]. 125I-labelled OTA bound with high affinity to membrane fractions of the rat testis (Ka = 13.8 +/- 1.25 litres/nmol), mammary tissue (Ka = 20.3 +/- 4.36 litres/nmol) and uterus (Ka = 27.8 +/- 0.74 litres/nmol). Competition studies with various OT and AVP receptor agonists and antagonists confirmed that the binding was to OT receptors. AVP receptors in the testis were found to be identical to AVP V1a receptors in the liver. The AVP receptor density in the testis was much higher than the OT receptor density (109 +/- 12.3 vs 5.2 +/- 0.79 (mean +/- S.E.M.) fmol/mg protein). Autoradiographical localization showed that both OT and AVP receptors were present in the interstitial spaces in the testis consistent with binding to Leydig cells. AVP receptors were also localized on the epithelial surfaces of the seminiferous tubules and on testicular blood vessels. This study has, for the first time, found OT receptors in the testis of the rat which have similar ligand-binding characteristics to mammary and uterine OT receptors. The receptor localizations are consistent with binding to Leydig cells.
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PMID:Characterization and localization of oxytocin receptors in the rat testis. 804 5

A synthetic 45-mer oligonucleotide corresponding to part of the ovine endometrial oxytocin receptor cDNA was hybridized to sections of ovine uterus collected from 40 ewes at different stages during the oestrous cycle, the first 3 weeks of pregnancy and seasonal anoestrus. The quantity of oxytocin receptor mRNA was measured as the optical density (OD) value on autoradiographs using image analysis. Message first appeared in the luminal epithelium on days 14-15 of the cycle, increasing to a peak OD of 0.48 at oestrus and decreasing again between days 2 and 5. Oxytocin receptor mRNA in the superficial glands, deep glands and caruncular stroma increased between day 15 and oestrous to peak OD values of 0.17, 0.11 and 0.11 respectively, declining again by day 2 and reaching basal values (OD < 0.015) by day 5. Hybridization to the myometrium tended to rise from a mean OD value of 0.01 on days 2-15 to a peak of 0.03 +/- 0.01 (mean +/- S.E.M.) on days 0-1, but the change was not significant. In pregnant ewes there was no detectable oxytocin receptor mRNA on days 14-15 in any region, but hybridization to the luminal epithelium was present in two of three ewes on day 21. In anoestrous ewes oxytocin receptor mRNA concentrations in all areas of the endometrium were approximately half those measured at oestrus. Optical density readings for oxytocin receptor mRNA in the various uterine compartments were compared with measurements of oxytocin receptors in the same regions as assessed by binding studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin (125I-labelled OTA). In the endometrium, receptor mRNA and 125I-labelled OTA binding patterns changed in parallel, and both sets of measurements were significantly correlated (P < 0.01). In the myometrium, a significant increase in 125I-labelled OTA binding occurred at oestrus; this was not accompanied by a similar increase in oxytocin receptor mRNA hybridization. This study helps to confirm that the previously identified cDNA clone is derived from the ovine oxytocin receptor, as patterns of oxytocin receptor mRNA expression in the endometrium closely resembled those of oxytocin binding. Maximum expression and binding both occurred at oestrus, suggesting that regulation of the oxytocin receptor gene in the uterus occurs principally at the transcriptional, rather than at the translational, level. Failure to detect a significant increase in myometrial mRNA expression at oestrus may indicate that the endometrial and myometrial oxytocin receptors are of different isoforms.
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PMID:Localization of oxytocin receptor mRNA in the ovine uterus during the oestrous cycle and early pregnancy. 818 18

Besides stimulating uterine myometrial and mammary myoepithelial cell contraction, oxytocin (OT) causes the release of prostaglandins (PGs) from uterine endometrium/decidua and amnion cells. Lacking information about OT receptors eliciting PG release, we don't know how they are related to OT receptors involved in smooth muscle contraction. The amnion offers great potential for characterizing OT receptors associated with PG release, as the amount of iodinated OT antagonist ([125I]OTA) bound to rabbit amnion membranes during labor is among the greatest of any tissue yet studied, reaching about 10 pmol/mg membrane protein. The relative affinities of several OT analogues for binding sites on amnion membranes are the same as those on decidual membranes. There are differences in the ligand profile between amnion and myometrium, but they could be due to the additional presence of vasopressin receptors on myometrial membranes. An increase in the sensitivity of PGE2 release from amnion cells in culture to OT and analogues accompanies the rise in OT receptor concentration at the end of gestation. Increases in [125I]OTA binding in vivo can be mimicked with cultured amnion cells by addition of agents that elevate intracellular cAMP levels. Based on the time course and inhibition of the increase with cycloheximide, cAMP might induce OT receptor gene expression. The increase also is reflected by a marked elevation in the covalent labeling of a 50-kDa electrophoretic band with a photoactivated derivative of [125I]OTA. Because of the homogeneity of cell types in the amnion, the ease of culturing amnion cells, and the high concentration of OT receptors that can be induced, this tissue should be very useful in characterizing OT receptors associated with PG synthesis.
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PMID:Oxytocin receptors and prostaglandin release in rabbit amnion. 839 66

Proximal separation (PS) refers to isolating pups in small cages so dams can hear, smell, and see pups but have very limited physical contact with them. Six days of PS diminished the number of discernible oxytocin- (OT) immunostaining perikarya in forebrain areas of rat dams compared with 6 days of total separation (TS) or no separation (NS) from pups. Dams exhibited a more rapid resurgence of maternal behavior after 4-6 days of PS than after 4-6 days of TS. Bilateral infusion of the OT antagonist (OTA; 1 microgram/microliter/side) into the ventral tegmental area blocked the resurgence of maternal behavior after 3-6 days of PS but not after 2 days of PS or 4-6 days of NS. The conclusion was that PS for 3 or more days reinstates OT as necessary and sufficient for the activation of maternal behavior in experienced rat mothers. These findings suggest that some aspects of somatosensory stimulation from pups regulate the role of OT in the control of maternal behavior.
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PMID:Interfering with somatosensory stimulation from pups sensitizes experienced, postpartum rat mothers to oxytocin antagonist inhibition of maternal behavior. 855 21

The entire coding region of an ovine endometrial oxytocin receptor (OTR) cDNA was generated by PCR, subcloned into the SV40 major late promoter expression vector pSVLJ and transiently expressed in Cos-7 cells. A specific OTR antagonist, 125I-labelled d(CH2)5 [Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin (OTA), was used to describe the binding kinetics of the expressed receptor which had a Kd of 4.5 nM and Bmax of 2.4 nM/mg protein (6.8 x 10(5) receptor molecules/transfected cell). The functional properties of the expressed OTR were determined by measuring oxytocin-induced phosphoinositide (PI) hydrolysis. Oxytocin increased PI turnover in OTR transfected cells fourfold in excess of residual endogenous activity, and stimulated phospholipase C (PLC) activity in a dose- and time-dependent manner, confirming that the expressed OTR cDNA was functional. Arginine vasopressin also stimulated PI turnover in a dose-dependent manner; thresholds of responses to oxytocin and arginine vasopressin were 10(-9) M and 10(-7) M respectively. OTA did not increase PI turnover and competitively inhibited the oxytocin-induced response. Direct activation of the pathway by aluminium fluoride and guanosine (3'-O-thio)-triphosphate (GTP gamma S) confirmed that the OTR was G-protein linked. Co-incubation of GTP gamma S with oxytocin shifted the PI-response threshold from 10(-7) M to 10(-9) M and significantly increased the level of response, suggesting that maximum PI turnover was agonist-dependent. The G-protein involved in mediating the signal transduction pathway was pertussis toxin-insensitive and, therefore, probably a member of the Gq subfamily. The PLC inhibitor, U73122, had no effect on oxytocin-induced PI turnover, consistent with the response in endometrial tissue. These data suggest that the signalling pathway mediated by expressed OTR is similar to that attributed to OTR occupancy in ovine endometrium.
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PMID:Functional characterisation of an ovine endometrial oxytocin receptor cDNA transiently expressed in Cos-7 cells. 869 Oct 97

Previous studies in the endometrium of ruminants showed that type I interferon (IFN) prevents oxytocin receptor (OTR) formation. We studied the effect of IFN-alpha on human myometrial cells in culture expressing a high density of biologically active OTR. We found that IFN-alpha induced a 35-50% decrease in OTR mRNA and protein and that this inhibition was time and dose dependent. Maximal inhibition of OTR mRNA was obtained after 2-3 days, whereas 1-(beta-mercapto-beta, beta-cyclopentamethyl-enepropionic acid,2-O-Me-Tyr,Thr4,Orn8,Tyr9-amide)-[125I]vasotocin ([125I]OTA) binding reached a nadir after 3-4 days, with half-maximal inhibitory concentration (IC50) = 1,100 U/ml. Mathematical analysis of multiple homologous competition curves for [125I]OTA indicated that IFN-alpha treatment (5,000 U/ml x 3 days) reduced just the binding capacity (Bmax) without changing the binding affinity. Accordingly, the same treatment with IFN-alpha did not affect the half-maximally effective concentration (EC50) for the oxytocin-induced increase in intracellular calcium but significantly decreased maximal responsiveness (Emax) of myometrial cells to OT stimulation. In conclusion, our data demonstrate, for the first time, a negative regulation by IFN-alpha of the steady-state expression of OTR mRNA in cultured human myometrial cells obtained from nonpregnant uteri. This inhibition was followed by a parallel decrease in both the Bmax for [125I]OTA and Emax for oxytocin, suggesting a decreased OTR protein availability.
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PMID:Interferon-alpha downregulates expression of the oxytocin receptor in cultured human myometrial cells. 894 70

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

Oxytocin (OT) is present in the mammalian testis and has been postulated to play a role in modulation of seminiferous tubule contractility. However, recent evidence suggests that the myoid cells responsible for such contractile activity do not express OT receptors. In this study computer-assisted analysis and time-lapse videomicrography were used to investigate the biological effects of neurohypophysial peptides and their analogues on seminiferous tubule contractility. Adult rat testes were placed in fresh oxygenated Dulbecco's modified Eagle's medium (DMEM) F12 medium, decapsulated and the tubules gently teased apart. A small section of tubule was placed in a microslide chamber and perifused with medium. Seminiferous tubules were treated with OT (2 nM), [Arg8]-vasopressin (AVP, 0.2 nM) or [Thr4,Gly7]-OT (TGOT, 2 nM, 8 nM and 0.2 microM). Specific antagonists were also given simultaneously with OT and AVP treatments. Data were analysed to give arbitrary units of contractility. Both OT and AVP increased tubule contractility, with AVP being at least 10 times more potent than OT. Treatment with the selective OT antagonist, desGly-NH2,d(CH2)5[d-Tyr2,Thr4]-ornithine vasotocin (OTA, 0.2 microM and 2 microM) significantly reduced OT-induced increases in seminiferous tubule contractility but had no effect on AVP-induced responses. In contrast, the AVP antagonist, Phaa-d-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (AVPA) was more potent at reducing AVP-induced increases than OT-induced responses. The selective non-peptide AVPA SR 49059 blocked the response to both peptides in a similar manner, whilst the non-peptide OTA L367,773 did not block OT-induced increases in seminiferous tubule contractility at doses that were slightly inhibitory to AVP-induced responses. The specific OT agonist TGOT did not induce a contractile response. The data in this study demonstrate that in the testis AVP acts via V1a receptors to stimulate contractile activity and suggest that OT may act via a receptor which differs from the classical V1a and uterine-type OT receptor. These findings support a role for OT in the regulation of seminiferous tubule contractility and raise the possibility that AVP may also be important in this process.
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PMID:Characterisation of the biological effects of neurohypophysial peptides on seminiferous tubules. 949 31


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