Disease relevance of Oxtr

• Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain [1].
• In trained WKY, baseline bradycardia (P<0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (+3.5-fold), without any change in OT receptor mRNA expression [1].
• To study the molecular mechanisms underlying OTR regulation, we have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the rat OTR gene, using sequence information derived from a human myometrial OTR cDNA [2].
• The existence of two OT receptor subtypes in the uterus has important implications in the clinical application of OT antagonists as tocolytics for preterm labor [3].
• The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats [4].

Psychiatry related information on Oxtr

• Acute stress responses, maternal behavior and central OT receptor binding in adult rats have been linked to the amount of maternal licking and arched back, upright nursing received during infancy [5].
• The bilateral injection of the oxytocin receptor antagonist, N-acetyl-2-O-methyl-tyrosine-oxytocin (AMTO), in the nucleus accumbens of male rats prevented oxytocin-enhanced grooming without affecting locomotor activity [6].
• Water deprivation for 12-48 h increased corticosterone and had a duration-dependent "anxiolytic" effect in the elevated X-maze, increasing the ratio of open/total arm entries (OTR) and the proportion of time spent on the open arms (% time) without affecting total entries [7].
• These findings suggest that individual differences in maternal behaviour may be directly related to variations in oxytocin receptor expression [8].

High impact information on Oxtr

• Inhibition of oxytocin receptor function by direct binding of progesterone [9].
• These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone [9].
• The selective oxytocin receptor agonist [Thr4, Gly7] oxytocin does not stimulate cAMP production in RIMCT cells but does promote PI hydrolysis [10].
• These studies demonstrate that AVP or a V2 receptor agonist stimulate PI hydrolysis in cultured RIMCT cells via occupancy of the oxytocin receptor [10].
• Moreover, when Tyr115 is replaced by an Asp and a Phe, the amino acids naturally occurring in the V2 and in the OT receptor subtypes, the agonist selectivity of the V1a receptor switches accordingly [11].

Chemical compound and disease context of Oxtr

• The OTR signaling mediated by oxytocin inhibited estrogen-stimulated growth of leiomyoma cells.Leiomyoma cells expressed many genes of the parturient myometrium, including OTRs, but were deficient in COX-2 expression [12].
• The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension [4].
• Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA [4].
• To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin [13].
• We conclude that compound 1 is a potent, selective, and orally active nonpeptide oxytocin receptor antagonist, which is a suitable candidate for evaluation as a potential tocolytic agent for the management of preterm labor [14].

Biological context of Oxtr

• Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term [15].
• Ultrastructural in situ hybridization combined with immunogold labeling indicated that pituitary OTR gene expression is highly cell-specific and restricted to lactotrophs [16].
• Here, we structurally characterized OT receptor (OTR) mRNA in mammary gland and analyzed its expression during gestation and lactation and in response to steroid treatment [17].
• During pregnancy, OTR mRNA per mammary gland increased approximately 150-fold and remained high during lactation, consistent with the previously identified regulation of OT binding sites and the role of OT during lactation [17].
• In summary, our data demonstrate a differential control of OTR expression in uterus versus mammary gland and a mammary gland-specific OTR mRNA polyadenylation site [17].

Anatomical context of Oxtr

• The abundance of OTR mRNA in the vena cava and pulmonary vein was associated with high atrial natriuretic peptide mRNA [18].
• Rat oxytocin receptor in brain, pituitary, mammary gland, and uterus: partial sequence and immunocytochemical localization [19].
• Several hours before the increase in OT receptor concentration, there was a proportional increase in estrogen receptor concentration in both the cytosol and nuclear fractions of the myometrium [15].
• In accordance with this finding, only the lactotroph-derived cell line MMQ expressed the OTR gene among several pituitary cell lines tested [16].
• Oxytocin receptor messenger ribonucleic acid: characterization, regulation, and cellular localization in the rat pituitary gland [16].

Associations of Oxtr with chemical compounds

• Using the selective OT receptor ligand compound VI, we detected a high number of OT-binding sites in the rat vena cava and aorta [18].
• In the perinatal period, the change in OT receptor concentration was proportional to the ratio of plasma estradiol to progesterone levels [15].
• Moreover, tamoxifen had no effect on the mammary gland OTR mRNA level [17].
• Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites [20].
• Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams [21].

Physical interactions of Oxtr

• Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1) [22].
• The present study shows that testosterone treatment of aging rats restores normal adult levels of OT receptor binding in the olfactory tubercle and in the hypothalamic ventromedial nucleus, but not in the caudate-putamen [23].

Regulatory relationships of Oxtr

• An extremely high proportion of neurons expressing either ER also coexpress mRNA for the oxytocin receptor (OTR) [24].
• As it is known that transforming growth factor-beta (TGF-beta) can be released from carrier proteins by acid or heat, TGF-beta1 and 2 were tested and found to induce an increase of OTR binding [25].
• The objective of the present study was to further elucidate our previous observation that beta2-adrenoceptor activation induces oxytocin receptor (OTR) expression in rat myometrium [26].

Other interactions of Oxtr

• It can be concluded from these results that during the estrous cycle, OTR mRNA levels in rat uterus predominantly increase at proestrus with a decrease in ERalpha and ERbeta mRNA levels, which is probably due to the increased estrogen levels in circulation before ovulation [27].
• For this, highly selective agonist and antagonist ligands of the OT receptor and nonselective agonist and antagonist ligands of the V1b receptor were employed [28].
• OTR and P4 receptor (PR) were measured using radioligand-binding assays [29].
• Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression [30].
• These data indicate that the reduced plasma testosterone found in 20-month old rats is responsible for the loss of OT receptors in the olfactory tubercle and hypothalamic ventromedial nucleus, whereas other aging-related mechanisms may account for the decrease of OT receptor binding in the caudate-putamen [23].

Analytical, diagnostic and therapeutic context of Oxtr

• In this study we show, by using Northern blot analysis, reverse transcriptase-polymerase chain reaction, and ultrastructural in situ hybridization that the same OTR gene is also expressed in the pituitary, where it gives rise to a 6.7- and a 4.8-kilobase messenger RNA [16].
• RT-PCR analysis did not provide any evidence for differences in the coding regions, suggesting that both uterine and mammary gland OTR mRNAs encode the same receptor protein [17].
• We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat [20].
• Estrogen treatment following OVX on day 18 of pregnancy caused increased OTR mRNA levels, whereas ovariectomy alone increased ERbeta mRNA but not ERalpha mRNA [31].
• DBS sections were processed for immunohistochemistry (polyclonal guinea pig anti-OT) or in situ hybridization for OT and OT receptor (35S-oligonucleotide probes) [1].

References