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

Specific receptors for oxytocin have been identified in rat forebrain. Previous studies have demonstrated that in select regions, these receptors are dependent on heterologous induction by gonadal steroids. To investigate whether brain oxytocin receptors are homologously regulated by oxytocin, we measured oxytocin receptor binding after hypothalamic paraventricular nucleus lesions, repeated central injections of oxytocin, and continuous central infusion of oxytocin via osmotic minipump. Neither lesions of the paraventricular nucleus nor repeated oxytocin injections altered the binding of the selective oxytocin receptor ligand [125I]OTA [125I] d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin, as measured by in vitro receptor autoradiography. After 10 days of continuous oxytocin infusion by osmotic minipump, oxytocin receptor binding decreased in every target field by at least 50%. This decrease appeared to represent a down-regulation of receptors and not displacement by exogenous peptide, as it persisted for at least 24 h after pump removal, and binding remained reduced in the presence of a saturating concentration of [125I] OTA. Reduction of oxytocin receptors in response to increased oxytocin release may represent an important physiological mechanism for the regulation of central oxytocin neurotransmission.
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PMID:Homologous regulation of brain oxytocin receptors. 131 51

The ability of astroglial cells to exhibit oxytocin (OT)-binding sites has been investigated in embryonic hypothalamic and hippocampic astroglial cell cultures. The differential characteristics of binding of OT and [Arg8]vasopressin (AVP) agonists and antagonists to the OT-binding sites using the highly selective iodinated OT antagonist d(CH2)5-[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT ([125I]OTA) have been evaluated using intact cells maintained for 12 days in culture. The specific binding displayed features of reversibility. Computer analysis of the saturation studies using the LIGAND program indicated that, at 4 degrees C, the antagonist binds to a homogeneous population of sites with a Kd value of 0.02 nM and a low binding-site density of around 2 fmol/dish for hypothalamic cells and 6 fmol/dish for hippocampic cells. For hypothalamic cells, competition curves using unlabelled OT, AVP or V2 AVP agonist were characterized by a pseudo-Hill coefficient below unity (0.7), indicating possible heterogeneity among the binding sites. On the other hand, the dose-inhibition curves resulting from competition studies with hippocampic cells had a pseudo-Hill coefficient close to unity, except for OT. Computer analysis (LIGAND) indicated that the OT dose-inhibition curve was significantly better fitted to a two-site model, and this can be explained by two apparent forms of the receptor having high and low affinities for the displacing drug. The relative potencies of the peptides tested for binding to the high-affinity site were: AVP greater than OT greater than V1 AVP antagonist ([d(CH2)5-Tyr(Me)2]AVP) = V2 AVP agonist greater than AVP-Sar ([d(CH2)5-Sar7,Arg8]VP) in hypothalamic cultures, and OT = AVP greater than V1 AVP antagonist greater than V2 AVP agonist in hippocampic cultures. In addition, autoradiography allowed visualization of OT-binding sites, which are located on both soma and processes of astrocyte-like type of cells. In conclusion, these data provide evidence that glial cell cultures contain specific OT-binding sites which display pharmacological characteristics different from those already reported in neuronal cultures and in the adult rat brain.
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PMID:Oxytocin receptors on cultured astroglial cells. Kinetic and pharmacological characterization of oxytocin-binding sites on intact hypothalamic and hippocampic cells from foetal rat brain. 131 31

Specific binding sites for the radio-iodinated oxytocin (OT) antagonist d(CH2)5-[Tyr(Me)2,Thr4, Tyr-NH2(9)]OVT ([125I]OTA) have been characterized on cultured hypothalamic astroglial cell membranes. The rate of association of the ligand to OT-binding sites was identical in the presence and the absence of the non-hydrolysable GTP analogue guanosine 5'-[beta gamma-imido]triphosphate (Gpp[NH]p, 0.1 mM), whereas the monophasic dissociation reaction became biphasic in the presence of Gpp[NH]p. Scatchard analysis of equilibrium binding of [125I]OTA resulted in a linear plot with a single class of binding sites (Kd 0.06 nM) which were insensitive to the addition of Gpp[NH]p. Unlabelled OT and [Arg8]vasopressin (AVP) bound to high- (H) and low- (L) affinity states with a dissociation constant ratio (KL/KH) of 100 for both hormones. Binding with both high and low affinity required the presence of Mg2+ in the incubation buffer, and the addition of Gpp[NH]p decreased the KL/KH ratio to 10 and increased the percentage of low-affinity binding sites. On the other hand, neither omission of Mg2+ from the buffer nor the addition of Gpp[NH]p altered the binding of either OT or V1 AVP antagonists to OT receptors. In the presence of a G-protein inactivator (N-ethylmaleimide; 3 mM) during OT competition studies the affinities of the two OT-binding sites were unchanged, but 90% of the high-affinity binding sites were converted into the low-affinity state. These results obtained with cultured hypothalamic astroglial cells provide further evidence for a coupling of OT receptors with a guanine-nucleotide-binding protein, with a requirement for Mg2+.
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PMID:Oxytocin receptors on cultured astroglial cells. Regulation by a guanine-nucleotide-binding protein and effect of Mg2+. 131 32

Using autoradiography on film, specific binding sites for arginine-vasopressin (AVP) and for oxytocin (OT) were localized in various areas of the brain of adult male guinea pigs. Vasopressin binding sites were detected with [3H]AVP or with [125I]VPA, a recently synthetized linear vasopressin antagonist radiolabeled with 125I. [125I]VPA and [3H]AVP yielded similar results, thus suggesting that AVP binding sites present in the guinea pig brain are V1 type receptors. Supporting evidence on this was obtained in competing studies using structural analogues allowing to discriminate V1 receptors from V2 and from OT receptors. Oxytocin binding sites were labeled with [3H]OT or with the iodinated OT antagonist [125I]OTA; both ligands yielded similar results. The localization in the guinea pig brain of AVP binding sites differed from that of OT binding sites. AVP binding sites were mainly detected in the olfactory bulb and throughout the cerebral cortex. Oxytocin binding sites were most noticeable in the hypothalamic ventromedial nucleus, in the amygdaloid complex and in restricted areas of the cerebral cortex. A comparison of the present data with those previously described in the rat, the mouse, the human and the hamster brain suggests that similar binding sites are present in these species, but that their anatomical distribution differs markedly. These data are discussed in relation to immunocytochemical and electrophysiological data which suggest that binding sites detected by autoradiography may represent, at least in part, functional neuronal receptors.
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PMID:Localization and characterization of binding sites for vasopressin and oxytocin in the brain of the guinea pig. 133 Feb 6

Although previous studies have demonstrated that exogenous administration of oxytocin (OT) enhances sexual receptivity in female rats, there is no compelling evidence that endogenous OT has a physiological role in the regulation of female sexual behavior. In the current studies we centrally administered d(CH2)5[Tyr(Me)2Thr4,Tyr-NH2(9)]ornithine vasotocin (or OTA), a selective OT receptor antagonist, to block endogenous OT in ovariectomized females primed with different levels of gonadal steroids. After OTA administration (100-1000 ng), females primed with estradiol benzoate (EB; 1 microgram) and progesterone (P; 250 micrograms) showed reductions in both receptive and proceptive behaviors. These effects of OTA were also evident, though less striking, in females primed with higher doses of EB (10 micrograms) and P (250 micrograms), but significant OTA effects were absent in females primed with EB (10 micrograms) alone. Thus, OTA appeared to attenuate P's facilitation of sexual behavior. Surprisingly, these behavioral effects of OTA administration were not apparent immediately, but emerged only when OTA was given with P 4-6 h before behavioral testing. To determine if these delayed, but lasting, behavioral effects were associated with OTA occupancy of the OT receptor, we measured OT receptor binding ex vivo using receptor autoradiography. Six hours after intracerebroventricular administration of OTA (1000 ng), OT receptor binding was reduced at least 75% in the ventromedial nucleus of the hypothalamus relative to control levels of binding. Thus, those OT receptors previously implicated in the regulation of sexual receptivity appear to be significantly blocked throughout the period of OTA's behavioral effects. Together, these studies lend support to the hypothesis that endogenous OT has a physiological role in the regulation of female sexual behavior.
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PMID:A selective oxytocin antagonist attenuates progesterone facilitation of female sexual behavior. 164 66

Oxytocin, when administered centrally, has been associated with the modulation of various social initiatives including maternal and sexual behaviors. The nature of these effects depends on gonadal hormone status. In the present experiments, we investigated the effects of centrally administered oxytocin on the behavior of pair-housed male squirrel monkeys during interactions with a familiar female monkey. Pairs of male squirrel monkeys established reliable and persistent dominance relationships with dominant males showing increased sexual and aggressive behavior as well as higher plasma concentrations of testosterone. Oxytocin (0.1, 1.0 micrograms) increased the sexual and aggressive behavior of dominant monkeys without affecting these measures in the subordinate monkeys. In contrast to these effects in the dominant monkeys, oxytocin increased associative and marking behaviors only in subordinate monkeys. Central administration of the oxytocin receptor antagonis d(CH2)5 [Tyr(Me)2, Thr4,Tyr-NH2(9)] OVT (OTA; 0.05 microgram) had no intrinsic effect on behavior but blocked the effects of exogenous oxytocin. To investigate further the specificity of oxytocin's effects on social behavior, we administered the structurally related peptide arginine vasopressin under identical conditions. Vasopressin (0.5, 5.0 micrograms) decreased social behaviors and increased motor activity in both dominant and subordinate monkeys. Previous studies in rodents have demonstrated that oxytocin receptors are induced by gonadal steroids in a regionally specific fashion. The status-related behavioral effects of oxytocin in the squirrel monkey may reflect differences in brain oxytocin receptor density associated with the higher concentrations of testosterone in the dominant animal. Alternatively, the status-related effects may depend on the conditioned behavioral differences associated with social organization.
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PMID:Social status in pairs of male squirrel monkeys determines the behavioral response to central oxytocin administration. 164 3

The present study was designed to determine the localization of the endometrial oxytocin receptor during the ovine oestrous cycle, particularly on day 14, the time of initiation of luteal regression in the ewe. Samples were obtained from 29 ewes at different stages of the oestrous cycle (several during the luteal phase and on every day between day 14 (-2) and day +3 of the oestrous period). Oxytocin receptors were localized autoradiographically in sections of uterine tissue, using the 125I-labelled oxytocin receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(ortho-methyl)-Tyr2,Thr4,Orn8, Tyr9-NH2]-vasotocin (125I-labelled OTA). There was some variation in the pattern of 125I-labelled OTA labeling between different uterine tissue samples from the same ewe and also between samples obtained from different ewes thought to be at the same stage of the oestrous cycle. A clear overall pattern did, however, emerge with 125I-labelled OTA-binding sites distributed between luminal epithelial cells, glandular epithelial cells and caruncular stromal cells to varying extents on different days of the cycle. During the luteal phase (days 5-12) clear specific labelling of endometrial tissue was generally absent. On day 14 labelling was evident on the luminal epithelium, but only in nine tissue samples out of a total of 18 studied, indicating that the entire luminal surface did not contain oxytocin receptors at this time. Between the day before oestrus and day 3 of the oestrous cycle the luminal epithelium was consistently labelled.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoradiographic localization of oxytocin receptors in the endometrium during the oestrous cycle of the ewe. 165 40

Several recent studies have suggested that the neurohypophyseal peptide oxytocin may have a role within the brain to mediate various forms of affiliative behavior. As the regulation of oxytocin function may be largely determined by the number and distribution of its membrane bound receptor, we investigated oxytocin receptor distribution in two Peromyscus species selected for differences in affiliative behavior. Using in vitro receptor autoradiography with the selective oxytocin receptor ligand [125I]d(CH2)5[Tyr(Me)2,Tyr-NH9(2)]OVT ([125I]OTA), we compared Peromyscus maniculatus, a polygamous species, to Peromyscus californicus, a monogamous species. Marked species differences in the distribution of [125I]OTA were apparent in several brain areas, including olfactory pathways, bed nucleus of the stria terminalis, amygdala, dorsal lateral septum, and several cortical regions. In addition, gender differences in the binding pattern were evident in several regions, mostly due to sexually dimorphic patterns in the polygamous species, P. maniculatus. To further compare these species, the binding of a [3H]arginine-vasopressin antagonist was assessed in alternate sections from those used for [125I]OTA. Relative to oxytocin receptors, binding to arginine-vasopressin receptors showed fewer species differences, although the monogamous species appeared to have more arginine-vasopressin receptors in the neocortex and lateral septum. The striking differences in oxytocin receptor distribution are consistent with earlier studies in other rodents, suggesting that oxytocin may have an important role for mediating species-typical patterns of social affiliation.
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PMID:The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. 165 22

A highly specific oxytocin receptor ligand, 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH9(2)] vasotocin (125I-OTA), was used to localize high affinity oxytocin receptors in ovine uterine and oviduct tissues throughout the oestrous cycle. The pattern of binding revealed by in vitro autoradiography correlated well with the results of the homogenate receptor assays using the same ligand and with previous binding assays using the tritiated ligand. At oestrus, specific 125I-OTA binding was evident on the luminal epithelium of the caruncular and intercaruncular regions, on the epithelial cells lining the secretory uterine glands and in the stroma underlying the caruncular epithelium. In the myometrium diffuse labelling was evident in the outer longitudinal smooth muscle layer. At Day 4 of the cycle, binding to the stroma was diffuse and virtually absent from the glandular epithelium. No specific binding was evident in either tissue at Day 12 of the luteal phase, but by Day 14, prior to the decrease in peripheral progesterone concentrations, binding was again apparent on the luminal epithelium only. Specific binding to the oviduct was localized to the smooth muscle layer of the isthmus region of oestrous ewes and was not detected at any other stage of the oestrous cycle. These studies extend our knowledge of the distribution of oxytocin binding sites in uterine and oviduct tissues throughout the oestrous cycle and suggest that oxytocin has an important role in stimulating oviduct and uterine motility at a time crucial to successful egg collection and/or sperm embryo transport.
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PMID:Autoradiographical localization of oxytocin binding sites on ovine oviduct and uterus throughout the oestrous cycle. 165 59

Several lines of evidence suggest that oxytocin modulates the formation and maintenance of social bonds. In the current experiments we investigated the influence of centrally and peripherally administered oxytocin on the behavior of 6-8 day old rat pups during brief periods of social isolation. Ultrasonic vocalizations emitted by isolated pups were decreased following i.c.v. administration of oxytocin, at doses (500, 1000 ng) which did not affect motor activity. S.c. administered oxytocin (1, 10 micrograms) produced a biphasic change in ultrasonic vocalizations, depending on dose. Central administration of the oxytocin antagonist (d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH2(9)]OVT) (OTA, 500 ng) did not measurably affect pup behavior by itself but did block the decrease in calls following central but not peripheral administration of oxytocin. These data demonstrate that oxytocin via its central receptor can regulate the response to social isolation.
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PMID:Central administration of oxytocin modulates the infant rat's response to social isolation. 166 88


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