Disease relevance of Oxt

• Oxytocin augments baroreflex bradycardia in conscious rats [1].
• OT treatment caused the rapid phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2 or p42MAPK), which was partially inhibited by pertussis toxin (PTX), consistent with OTR-Gi coupling [2].
• Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain [3].
• Whereas depletion of serotonin with p-chlorophenylalanine (PCPA) blocked the increase in hypothalamic levels of AVP and OT mRNA following osmotic stimuli in rats (2% saline drinking or dehydration), the increase in mRNA size was similar in PCPA and control animals [4].
• 1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo [2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperaz ine (L-368,899): an orally bioavailable, non-peptide oxytocin antagonist with potential utility for managing preterm labor [5].

Psychiatry related information on Oxt

• Oxytocin antiserum delays onset of ovarian steroid-induced maternal behavior [6].
• In both wehicle- or melatonin-treated rats, food and water deprivation did not affect the OT, PRL and ACTH secretion [7].
• These results suggest that 6-h selective RSD may not be sufficient to induce the activation of the hypothalamo-pituitary adrenal axis, and that the expression of the galanin gene in the hypothalamus reacts more readily against the loss of REM sleep in comparison to other hypothalamic neuropeptides such as arginine vasopressin, oxytocin and orexins [8].
• Influence of exogenously administered oxytocin on the corticosterone and prolactin response to psychological stress [9].
• The results of this study revealed that food deprivation for 48 h produced little change in OT concentration in the various hypothalamic nuclei studied, including the paraventricular and supraoptic nuclei, with the exception of the median eminence (ME), where a significant decline (-36%; p < 0.05) was detected [10].

High impact information on Oxt

• Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration [11].
• In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides [11].
• Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney [11].
• Finally, mobilization of intracellular Ca(2+) can also prime the releasable pool of oxytocin in the dendrites [12].
• Inhibin beta in central neural pathways involved in the control of oxytocin secretion [13].

Chemical compound and disease context of Oxt

• We have previously reported that intracerebroventricular (ICV) administration of oxytocin (OXY) produces a significant increase in maternal behavior in ovariectomized (OVXed) rats given a single priming dose of estrogen [6].
• Dehydration stimulates hypothalamic gene expression of histamine synthesis enzyme: importance for neuroendocrine regulation of vasopressin and oxytocin secretion [14].
• Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats [15].
• In the NRS-treated group, plasma levels of OT, AVP and immunoreactive glucagon (IRG) were significantly elevated 10 min after hemorrhage (2.3 ml/100 g body weight over 5 min) whereas hyperglucagonemia was not detected in the antiserum-treated group until 30 min posthemorrhage [16].
• Chronic hyponatremia is known to cause inhibition of pituitary vasopressin (AVP) and oxytocin (OT) secretion in response to most physiological stimuli, as well as a marked inhibition of synthesis of these peptides [17].

Biological context of Oxt

• Whereas steady state levels of OT mRNA were markedly increased throughout lactation, those of AVP mRNA were only transiently (initially) elevated, and the blood levels of these hormones were not significantly altered in lactating as compared with cycling virgin and postlactating rats [18].
• Rat myometrium exhibited a marked rise in the concentration of oxytocin (OT) receptors during parturition [19].
• Although specific OT receptors have been identified in anterior pituitary membranes, the structure and cellular localization of these binding sites have not been elucidated [20].
• This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of 5alpha-reductase isoforms I and II [21].
• Oxytocin (OT) is present in the male reproductive tract, where it is known to modulate contractility, cell growth, and steroidogenesis [21].

Anatomical context of Oxt

• These observations suggest a central site of action for VIP in OT and AVP release, probably in the hypothalamus [22].
• In view of the known action of estrogens in increasing the concentration of OT receptors in rat uterus, we propose that the following sequence of events occurs in the initiation of labor in the rat [19].
• Neurosecretory OT cells of the hypothalamic paraventricular nucleus that express VIP receptors were identified by using immunocytochemical techniques in combination with the retrogradely transported neuronal tracer Fluoro-Gold (iv injected) [23].
• Furthermore, posterior pituitary PRF partitioned in nearly equal amounts across 1K membranes, as did AII and OT [24].
• When 3 micrograms VIP were injected into the third ventricle of conscious ovariectomized rats, a significant (P less than 0.005) and transient elevation of plasma oxytocin (OT) levels was observed [25].

Associations of Oxt with chemical compounds

• Novel radioiodinated ligands for the detection of neurohypophyseal hormone receptors, with a high specific radioactivity and affinity, enabled the selective detection of OT receptors in the thymus and vasopressin (VP) receptors in the spleen [26].
• This increased concentration of estrogen receptors and their occupancy by estradiol stimulates the appearance of more OT receptors, which then trigger labor by interacting with circulating OT [19].
• The posterior pituitary content of immunoreactive AVP was 2500-fold higher in HZ rats, but the contents of dopamine and oxytocin were similar [27].
• Oxytocin, vasoactive-intestinal peptide, and serotonin regulate the mating-induced surges of prolactin secretion in the rat [28].
• Histamine stimulates c-fos expression in hypothalamic vasopressin-, oxytocin-, and corticotropin-releasing hormone-containing neurons [29].

Physical interactions of Oxt

• The oxytocin (OT) receptor of the lactating rat mammary gland was further characterized by radioligand binding and functional assays in vitro and compared to the uterine OT receptor [30].
• Competition studies with various OT and AVP receptor agonists and antagonists confirmed that the binding was to OT receptors [31].
• In addition to these differences in the regulation of biosynthesis and processing, AVP peptides were axonally transported to the pituitary 3 d earlier than OT peptides, and in far greater (20-fold) abundance [32].
• The uterus was removed 24-48 h after balloon insertion, and OT binding to the particulate fraction as well as nuclear estrogen and cytosolic estrogen receptor concentrations were determined [33].
• Because estrogens also increase OT receptor binding in male rats, it is possible that TP affects OT binding after being converted by aromatase to estradiol [34].

Co-localisations of Oxt

• Moreover, AVP and AVP mRNA were found to be colocalized with oxytocin in a few neurons [35].
• Increased nitrotyrosine was accompanied by an elevation of the apoptotic index in the old rats (SON: 11.01 +/- 3.33 vs. 0.57 +/- 0.50, p < 0.001; PVN: 3.08 +/- 1.12 vs. 0.42 +/- 0.32; POA: 6.60 +/- 1.93 vs. 0.18 +/- 0.17, p < 0.01; ARC: 0.001 +/- 0.0001 vs. 4.33 +/- 2.33). iNOS staining co-localized with GnRH and oxytocin staining [36].
• 1. Cholecystokinin is co-localized within the oxytocin- and, to a lesser extent, vasopressin-synthesizing magnocellular neurones in the hypothalamic supraoptic and paraventricular nuclei [37].
• GluR3 immunoreactivity co-localized to oxytocin-containing, but not vasopressin-containing, neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus and accessory magnocellular nuclei [38].
• Multiple labellings showed galanin and galanin messenger RNA to be co-localized with oxytocin messenger RNA in neurones of the dorsomedial part of the supraoptic nucleus during lactation [39].

Regulatory relationships of Oxt

• Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion [25].
• Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term [19].
• In conclusion, OT can downregulate V2R mRNA expression and upregulate AQP2 mRNA expression in the collecting duct as an agonist of the V2R like AVP [40].
• AVP (n = 9) and OT (n = 8) induced increases in [Ca2+]i were completely blocked by the V1A-receptor antagonist d(CH2)5Tyr(Me)2AVP [41].
• OT-stimulated c-fos expression was also mediated by ERK2 phosphorylation [2].

Other interactions of Oxt

• We propose that VIP and 5-HT are continuously active oscillatory neurotransmitters regulating OT release into pituitary portal blood and that these daily events only eventuate in PRL release when the mating stimulus has release the lactotroph from the inhibitory effects of dopamine [42].
• 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 [43].
• Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN [44].
• Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way [45].
• The influence of a subcutaneous injection of 20 microg OT on V2R and AQP2 mRNA expression is comparable to that of 10 microg AVP that we documented in the previous study [40].

Analytical, diagnostic and therapeutic context of Oxt

• Reverse-phase HPLC of aorta and vena cava extracts revealed a single peak corresponding to the amidated OT nonapeptide [46].
• Reverse-transcribed PCR confirmed OT synthesis in these tissues [46].
• In addition, the identity of the HA-stimulated neurons was investigated by dual antigen immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing increased c-fos expression [29].
• Real-time RT-PCR determined that OT treatment significantly reduced expression of 5alpha-reductase I but significantly increased 5alpha-reductase II expression in the ventral prostate [21].
• Characterization of oxytocin-binding sites in primary rat brain cell cultures [47].

References