Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of [3H]oxytocin binding sites among various subcellular fractions of rat myometrium paralleled the distribution of 5'-nucleotidase, a plasma membrane marker enzyme, but not of NADPH-cytochrome c reductase or succinate-cytochrome c reductase, which are endoplasmic reticulum and mitochondrial marker enzymes respectively. [3H]Oxytocin binding to the most enriched plasma membrane fraction showed the degree of selectivity with respect to hormone analogues that is expected for the oxytocin receptor. The binding of oxytocin to this fraction showed an apparent Kd of 1.98 X 10(-9) M and a capacity of 1.28 pmol mg-1. It is concluded that the oxytocin receptor is located on the plasma membrane of the smooth muscle cells of the rat uterus.
 ...
PMID:Localization of the oxytocin receptor in the plasma membrane of rat myometrium. 20 28

The demise of the corpus luteum is brought about by an interaction between ovarian oxytocin and uterine prostaglandin F2 alpha (PGF2 alpha) release in sheep. Indirect evidence suggests that a similar, but intra-ovarian, mechanism may also be involved in luteal regression in primates. During early pregnancy, a specific class of interferon (omega interferon) is released from the developing embryo in sheep and this interferon inhibits pulsatile release of uterine PGF2 alpha. Studies in ovariectomized, steroid-treated ewes indicate that conceptus secretory proteins inhibit pulsatile secretion of PGF2 alpha directly via an effect on prostaglandin synthesis and indirectly by maintaining plasma progesterone concentrations that inhibit the development of endometrial oxytocin receptors which normally occurs at the time of luteolysis. As pregnancy progresses, there is an increase in basal secretion of PGF2 alpha and PGE2 from the uterus into the fetal and maternal circulation. The release of maternal PGF2 alpha, but not PGE2, in response to oxytocin is also increased in late pregnancy. Endometrial oxytocin receptor concentrations follow a similar pattern, except at parturition where there appears to be downregulation of receptors. However, the release of PGF2 alpha in response to oxytocin remains high at this time and is further increased if the progesterone receptors are blocked with the anti-progestin RU486. The dissociation between oxytocin receptor numbers and release of prostaglandins in response to oxytocin is also observed under other physiological situations, such as during seasonal anoestrus and after long-term ovariectomy, and requires further investigation. The role of oxytocin in the initiation of labour remains controversial. Although oxytocin concentrations in maternal and fetal plasma are not increased until parturition, uterine oxytocin receptor concentrations, uterine activity and maternal PGF2 alpha release in response to oxytocin are high in late pregnancy. Uterine activity and PG release is not altered by oxytocin in the fetal circulation at any stage of late gestation. We have used the oxytocin analogue CAP to investigate further the possible role of oxytocin in the initiation of labour. CAP can inhibit oxytocin-induced PGF2 alpha release in cyclic sheep, at luteolysis, and in late pregnant sheep by binding to, and blocking, uterine oxytocin receptors. CAP does not inhibit basal fetal or maternal PGF2 alpha or PGE2 concentrations in late pregnancy or at parturition. CAP inhibits oxytocin-induced uterine activity and delays, but does not prevent, the increase in uterine activity associated with labour in this species.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Oxytocin and prostaglandin interactions in pregnancy and at parturition. 130 35

Just before the onset of labour, uterine myometrium becomes extremely sensitive to oxytocin, for which it is a primary target tissue, because of a dramatic increase in the number of oxytocin receptors. We report here the structure and expression of the human oxytocin receptor complementary DNA isolated by expression cloning. The encoded receptor is a 388-amino-acid polypeptide with 7 transmembrane domains typical of G protein-coupled receptors. The oxytocin receptor, expressed in Xenopus oocytes, specifically responds to oxytocin and induces an inward membrane current. Messenger RNAs for the receptor are of two sizes, 3.6 kilobases in breast, and 4.4 kilobases in ovary, uterine endometrium and myometrium. The mRNA level in the myometrium is very high at term. We conclude that the increase in receptor number in the myometrium at labour is, at least in part, due to the increase in mRNA.
 ...
PMID:Structure and expression of a human oxytocin receptor. 131 46

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.
 ...
PMID:Homologous regulation of brain oxytocin receptors. 131 51

The interaction between oestrogen and progesterone in the regulation of the uterine oxytocin receptor in sheep was evaluated by measuring the binding of oxytocin to membrane preparations of caruncular and intercaruncular endometrium and myometrium. Ovariectomized ewes were assigned in groups of five to each cell of a 4 x 2 factorial design. The four treatments were (a) vehicle (maize oil) for 12 days, (b) progesterone (10 mg day-1) for 9 days, (c) progesterone for 9 days followed by maize oil until day 12 and (d) progesterone for 12 days. The two oestradiol treatments consisted of the administration of implants in the presence or absence of oestradiol. The ewes were killed on day 10 (group b) or day 13 (groups a, c and d) for collection of uterine tissues. The response of the caruncular and intercaruncular endometrium to the treatments was similar. In the absence of oestradiol, treatment with progesterone continuously for either 9 or 12 days reduced the concentration of the oxytocin receptor in comparison with both the control and the progesterone withdrawal group (in which values were similar). The presence of oestradiol reduced the receptor concentrations in control and both 9- and 12-day continuous progesterone treatment groups, but enhanced the concentration in the progesterone withdrawal group. The myometrial oxytocin receptors responded in a similar way to those in the endometrium to progesterone treatment alone, but the addition of oestradiol produced no further effect. In conclusion, progesterone and oestradiol caused downregulation of the endometrial oxytocin receptor. On the other hand, progesterone withdrawal, similar to that which occurs during luteolysis, increased receptor density in the presence of oestradiol. Progesterone may influence the response of the myometrium to oxytocin by causing a reduction in receptor density.
 ...
PMID:Role of progesterone and oestradiol in the regulation of uterine oxytocin receptors in ewes. 131 47

In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.
 ...
PMID:Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy. 131 33

The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor expression in brain. By in vitro receptor autoradiography with an iodinated oxytocin analogue, specific binding to brain oxytocin receptors was observed in both the monogamous prairie vole (Microtus ochrogaster) and the polygamous montane vole (Microtus montanus). In the prairie vole, oxytocin receptor density was highest in the prelimbic cortex, bed nucleus of the stria terminalis, nucleus accumbens, midline nuclei of the thalamus, and the lateral aspects of the amygdala. These brain areas showed little binding in the montane vole, in which oxytocin receptors were localized to the lateral septum, ventromedial nucleus of the hypothalamus, and cortical nucleus of the amygdala. Similar differences in brain oxytocin receptor distribution were observed in two additional species, the monogamous pine vole (Microtus pinetorum) and the polygamous meadow vole (Microtus pennsylvanicus). Receptor distributions for two other neurotransmitter systems implicated in the mediation of social behavior, benzodiazepines, and mu opioids did not show comparable species differences. Furthermore, in the montane vole, which shows little affiliative behavior except during the postpartum period, brain oxytocin receptor distribution changed within 24 hr of parturition, concurrent with the onset of maternal behavior. We suggest that variable expression of the oxytocin receptor in brain may be an important mechanism in evolution of species-typical differences in social bonding and affiliative behavior.
 ...
PMID:Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. 132 30

A new structural class of cyclic hexapeptide oxytocin antagonists derived from Streptomyces silvensis and typified by L-365,209 (cyclo-[L-prolyl1-D-phenylalanyl2-L- isoleucyl3-D-dehydropiperazyl4-L-dehydroperazyl5-D-(N- methyl)phenylalanyl6]) was recently reported. In this paper we further delineate the structure-activity profile for this new class by systematic study of L-365,209 analogs obtained by total synthesis. The optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical 5- and 6-positions maintained good receptor affinity and also had useful levels of water solubility for intravenous formulation. By combining potency- and solubility-enhancing substitutions, several analogs were identified that have the desired combination of properties in vitro (22, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L-pipeco lyl-D- histidyl]; 25, cyclo-[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L -pipecolyl-D- histidyl]; 26, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-dehydropiperazyl-L-++ pipecolyl-D-histidyl]; 33, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L- piperazinylcarboxy-D-(N-methyl)phenylalanyl]; 34, cyclo-[L-prolyl-D-phenylalanyl-L-isoleucyl-D-dehydropiperazyl-L-or nithyl- D-(N-methyl)phenylalanyl]). In general, this class exhibited good selectivity for binding to the oxytocin receptor versus the arginine vasopressin V1a and V2 receptor subtypes, although increased V2 receptor affinity was observed in one case (32, cyclo[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L- lysyl-D-(N- methyl)phenylalanyl]). Unexpectedly, compound 33 was found to stimulate contractions of the isolated rat uterus via activation of the uterine bradykinin receptor. Compounds 22, 25, 26, 33, and 34 were found to be potent antagonists of oxytocin-stimulated contraction of the rat uterus in vitro and in vivo. Compounds 22 and 25 were additionally characterized as potent antagonists of oxytocin-stimulated uterine contractions in the near-term pregnant rhesus monkey. These studies thus demonstrate the selectivity and efficacy of certain members of this novel class of antagonists and suggest their use as pharmacological tools in further defining the role of oxytocin in both term and preterm labor.
 ...
PMID:Development of a novel class of cyclic hexapeptide oxytocin antagonists based on a natural product. 133 48

This study tested the hypothesis that the administration of oxytocin in doses equivalent to endogenous concentrations at and around oestrus could affect uterine and oviductal muscular activity at the time of gamete transport. Four ewes were fitted with recording electrodes in the left ampulla, ampullary-isthmic junction, utero-tubal junction and uterine horn. After surgical recovery, recordings from conscious free-standing animals were made for up to 10 h per day from Day -3 to Day +3 relative to oestrus in each ewe. Daily blood samples were taken for progesterone radioimmunoassay, and a vasectomized ram used to assess oestrus. A range of physiological doses of oxytocin (10-100 mU), or control saline injections were given intravenously. Electromyographic (EMG) activity was measured before and after injections. Spontaneous activity throughout the reproductive tract was low on Day -3 but increased to peak at oestrus (P < 0.05), when the pattern of activity consisted of short (2-10 s) co-ordinated high amplitude bursts (2-5 min-1). After oestrus, as overall activity declined, longer episodes of activity appeared but these occurred with a much slower frequency (1-4 h-1). Responsiveness to oxytocin was greatest on the day of oestrus at all electrode sites. Elevated responsiveness (relative to Day -3, the late luteal phase) was seen from Day -1 to Day +2 at the ampullary-isthmic junction and uterus, but on the day of oestrus only at the ampulla and utero-tubal junction. Duration of increased EMG activity after oxytocin injection ranged from 5 to 20 min. These results show for the first time that the uterine and oviductal musculatures of the ewe in vivo reached a peak in sensitivity to physiological concentrations of oxytocin at oestrus. When combined with information on oxytocin receptor populations and endogenous circulating concentrations, this suggest that endogenous oxytocin could influence oviduct and myometrial activity at this time.
 ...
PMID:Effect of oxytocin on the pattern of electromyographic activity in the oviduct and uterus of the ewe around oestrus. 133 35

The pulsatile release of oxytocin from the corpus luteum in the sheep is responsible for the pulsatile release of prostaglandin F2 alpha (PGF2 alpha) from the uterus at luteolysis. It has been proposed that PGF2 alpha also reinforces this process by stimulating the release of oxytocin from the corpus luteum. It is, however, unlikely that PGF2 alpha is the major stimulus for oxytocin release at this time. Although the stimulus for the pulsatile release of oxytocin from the corpus luteum appears to reach the ovary from the peripheral circulation, the nature of the stimulus is unknown. Pulses of oxytocin originating from the corpus luteum have also been observed during early pregnancy, but the release of PGF2 alpha, in response to this signal, is abrogated in some way by ovine trophoblast protein-1 (oTP-1). This protein has been shown to inhibit endometrial prostaglandin production and to decrease the amount of PGF2 alpha released in response to oxytocin. Reduction of uterine oxytocin receptor concentrations by conceptus secretory proteins or by interferons related to oTP-1 remains equivocal. Inhibition of uterine oxytocin receptors is, however, probably the major mechanism that prevents luteal regression during early pregnancy. In cyclic sheep the specific inhibition of uterine oxytocin receptors by 1-deamino-2-D-Try (oET)-4-Thr-8-Orn-oxytocin (CAP), a synthetic oxytocin receptor antagonist, inhibits luteal regression and suppresses pulsatile, but not basal, secretion of uterine PGF2 alpha. Thus, the effects of CAP directly parallel the endocrinological changes that occur in early pregnancy in the sheep.
 ...
PMID:Interaction between oxytocin and prostaglandin F2 alpha during luteal regression and early pregnancy in sheep. 133 37


1 2 3 4 5 6 7 8 9 10 Next >>