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

The maternal roles of oxytocin (OT) are well known, but recent work suggests that OT is also a vital component in fluid balance regulation. To explore the role of OT in salt/volume regulation, we studied NaCl intake in a genetically modified mouse strain lacking OT. Using male control and OT knockout mice (OTKO), we determined the circadian pattern of salt and water intake under need-free conditions. For the study of intake, a two-bottle choice system was used to provide access to water and 2% NaCl with computerized monitoring of licking activity. Salt licking activity (licks/24 h) for controls was 59 +/- 22 vs. 380 +/- 105 in OTKO (P < 0.05). The volume of salt consumed (ml/24 h) was 0.4 +/- 0.1 in controls vs. 1.8 +/- 0.4 in OTKO (P < 0.01). There was no statistical difference in the consumption of water between the groups. However, the initiation of water intake was shifted, with an advancement of almost 3 h in OTKO (P < 0.01). Differences in the timing of salt intake could not be determined due to the low volume of salt consumed by controls. Taken together, these data show that removal of OT amplifies the salt-seeking behavior associated with normal daily fluid fluctuations. The fact that OTKO voluntarily consume a normally aversive salt solution further implies that OT is a powerful regulator of circadian salt appetite.
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PMID:Enhanced salt intake in oxytocin deficient mice. 1157 85

We previously found stress-reduction in rats exposed to an oxytocin-injected cage-mate. Olfactory impairment and oxytocin antagonist treatment blocked the effect. Here, we investigated effects of social stress on the exposure-induced response and exposure on amygdaloid oxytocin concentrations. CT concentrations in exposed olfactorily impaired, CT antagonist-treated and saline-injected unexposed rats were reduced, compared to the significantly higher level in untreated and exposed saline-injected rats. Saline injections and group mixing enhanced heat dissipation. Exposure abolished the injection-induced, but not mixing-induced stress response, most likely via a social stress induced effect on the oxytocin-injected rat. The difference in exposure responsivity may relate to recognition, stress type and intensity affecting different stress-response systems. The mechanism could reinforce social attachment.
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PMID:Social stress blocks energy conservation in rats exposed to an oxytocin-injected cage mate. 1216 65

To explore the role of oxytocin in the regulation of salt appetite and blood pressure, we conducted studies in oxytocin gene-knockout mice and determined (1) blood pressure and heart rate during day and night periods, (2) salt appetite after iso-osmotic volume depletion, and (3) salt appetite and blood pressure after central injection of angiotensin II. Long-term arterial catheters were inserted, and blood pressure and heart rate were recorded for 24 hours. There was a modest decrease in blood pressure and heart rate in knockout mice. Salt appetite was measured with a 2- bottle choice (water and 2% NaCl), with measurement of licking activity. Mice were injected subcutaneously with 30% polyethylene glycol (0.5 mL), and voluntary intakes were measured for 24 hours. Knockout mice consumed 3 times the amount of NaCl than did controls, 276+/-77 vs 90+/-38 licks/24 h (P<0.05). Water consumption was similar between groups. Angiotensin II (5, 50, and 200 ng/3 microL) injected intracerebroventricularly produced dose-related increases in intake, with no differences between the groups. The 50-ng dose of angiotensin II elicited salt and water intakes of 151+/-43 vs 160+/-33 licks and 250+/-53 vs and 200+/-51 licks, respectively (control vs knockout). The pressor response to angiotensin II was not different between the groups. Results suggest that oxytocin plays a role in the regulation of blood pressure and salt appetite, specifically as mediated by volume receptors, and that the renin-angiotensin system is not involved in these changes.
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PMID:Salt appetite and the renin-angiotensin system: effect of oxytocin deficiency. 1295 13

Results from previous studies indicate that oxytocin (OT)-containing neural pathways are activated in laboratory rats after systemic administration of CCK or d-fenfluramine and that centrally released OT may participate in the anorexigenic effects of these treatments. To explore the relationship between feeding behavior and OT function, the effects of CCK and d-fenfluramine on feeding and central c-Fos expression were compared in wild-type (OT+/+) and OT-deficient mice (OT-/-) of C57BL/6 background. Male OT+/+ and OT-/- mice were administered saline or CCK (1, 3, or 10 microg/kg ip) after overnight food deprivation. Saline-treated OT+/+ and OT-/- mice consumed equivalent amounts of food after an overnight fast. CCK inhibited deprivation-induced food intake in a dose-dependent manner to a similar extent in both genotypes. CCK treatment also induced similar hindbrain and forebrain patterns of increased c-Fos expression in mice of both genotypes. After treatment with d-fenfluramine (10 mg/kg ip), both OT+/+ and OT-/- mice consumed significantly less food than untreated controls, with no difference between genotypes. We conclude that OT signaling pathways are unnecessary for the anorexigenic effects of systemically administered CCK and d-fenfluramine in C57BL/6 mice.
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PMID:Cholecystokinin and D-fenfluramine inhibit food intake in oxytocin-deficient mice. 1455 35

We used comparative genetics to investigate the location, structure and evolution of the oxytocin and vasopressin gene regulatory regions. The pufferfish, Fugu rubripes, is an attractive vertebrate model for comparison because of its maximal evolutionary distance from mammals and short intergenic regions. To determine whether regulatory DNA is conserved between oxytocin and vasopressin, and their Fugu homologs, isotocin and vasotocin, we generated transgenic mice bearing overlapping Fugu cosmids that contained the isotocin and/or vasotocin genes as well as short isotocin (5 kb) and vasotocin (9 kb) constructs. Our study shows that the Fugu isotocin and vasotocin genes express specifically in the mouse oxytocinergic and vasopressinergic neurones, respectively, and that the cis-regulatory elements which mediate neurone-specific expression are located within the short transgene constructs tested. Thus, the neurone-specific expression of the oxytocin and vasopressin gene families, and the mechanisms mediating the cell-specificity, evolved before the divergence of the fish and mammalian lineages. Salt-loading of transgenic mice induced an increase in abundance of isotocin, but not vasotocin mRNA in the cognate neurones. It appears that either the vasotocin gene does not respond to osmotic perturbations or the vasotocin transgene construct tested lacks osmotic response elements. Comparisons of homologous flanking sequences of the Fugu and mouse genes identified several short matching sequences, which are candidate regulatory elements.
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PMID:Neurone-specific expression and regulation of the pufferfish isotocin and vasotocin genes in transgenic mice. 1462 32

Our objective was to test the hypothesis that the cGMP signal-transduction mechanism mediates nitric oxide's (NO) modulation of oxytocin (OT) and vasopressin (VP) secretion from the hypothalamo-neurohypophysial system. Three studies were conducted in adult male Sprague-Dawley rats: (1a) Euhydrated rats received an intracerebroventricular (icv) infusion (1 microl/min for 30 min) of artificial cerebrospinal fluid (aCSF), vehicle (2.6% dimethyl sulfoxide [DMSO]) or 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (0.05 microg/microl), an inhibitor of soluble guanylyl cyclase (sGC). ODQ did not affect basal levels of plasma VP or OT; (1b) Rats dehydrated for 24 h received aCSF or 8-Br-cGMP (icv), a membrane-permeable analog of cGMP, and plasma hormones were measured 2 min later. 8-Br-cGMP did not significantly change VP or OT levels; (2) Rats ingested water or 2% NaCl for 4 days, and NO synthase (NOS) and sGC activities were measured in posterior pituitaries, the anatomical site of hormone secretion. Salt loading enhanced (P < 0.001) production of [(14)C]citrulline, the coproduct of NO synthesis, without altering cGMP; (3) One SON was microdialyzed with [(14)C]arginine and NOS and sGC activities were quantified in microdialysates during intravenous (iv) infusion of isotonic or hypertonic saline in awake and anesthetized rats. In awake rats, [(14)C]citrulline recovery, but not cGMP, increased (P < 0.05) during intravenous infusion of both isotonic and hypertonic solutions, and after insertion of microdialysis probe itself. In anesthetized rats, however, where basal NOS activity is low, intravenous infusion of hypertonic, but not isotonic solution, increased [(14)C]citrulline recovery without affecting cGMP. Thus, in the forebrain, neither NO produced basally nor during osmotic stimulation depends on cGMP to modulate plasma vasopressin and oxytocin secretion.
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PMID:NO inhibition of the magnocellular neuroendocrine system in rats is independent of cGMP signaling pathway. 1476 77

Accumulating evidence suggests that both oxytocin and arginine vasopressin (AVP) are vital components in the regulation of body fluid balance. However, the physiological role of oxytocin and possible cooperative interactions between oxytocin and AVP in sodium balance remain obscure, even though recent studies using oxytocin knockout (OTKO) mice suggested that oxytocin may contribute to the regulation of salt appetite. In the present study, we examined the effects of salt loading (drinking 2% NaCl for 5 days) on the expression of the AVP gene in the paraventricular (PVN) and supraoptic nuclei (SON) of wild-type, OTKO and heterozygous littermates using in situ hybridization histochemistry. In addition, the effects of salt loading on the expression of the oxytocin gene were also examined in wild-type and heterozygous mice. Under the non salt-loaded condition, the levels of AVP mRNA in the PVN and SON of OTKO mice were significantly decreased compared to those in wild-type mice. Nevertheless, the up-regulation of the expression of the AVP gene in response to salt loading was preserved in OTKO mice. The degree of the up-regulation in OTKO mice tended to be greater compared to those in wild-type mice, suggesting compensatory up-regulation of the expression of the AVP gene in OTKO mice after salt loading. The basal levels of oxytocin mRNA in the PVN and SON of heterozygous mice were significantly lower than those in wild-type mice. Salt loading caused an increase of oxytocin mRNA levels in the PVN and SON of both wild-type and heterozygous mice. The ratios of increase of oxytocin mRNA levels were very similar between wild-type and heterozygous mice, suggesting that the single remaining oxytocin gene in heterozygous mice responds normally to an osmotic cue. Finally, salt loading tended to increase the serum concentration of sodium regardless of genotype, and there were no genotype differences in both the control and salt-loaded groups. These results suggest ways in which oxytocin may play a cooperative role together with AVP in the regulation of sodium balance.
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PMID:Expression of the arginine vasopressin gene in response to salt loading in oxytocin gene knockout mice. 1496 74

Dense-cored vesicles (DCVs) containing oxytocin or vasopressin are secreted from both the nerve terminals in the posterior pituitary and dendrites in the hypothalamus of magnocellular supraoptic neurons. Dendritic secretion can be enhanced (primed) by pretreatment with either thapsigargin or oxytocin for subsequent activity-dependent release. Here, we determined whether priming involves a translocation of DCV closer to the dendritic membrane. To reduce total vesicle content, rats were salt-loaded for 24 h before application of thapsigargin or vehicle onto the ventrally exposed surface of the supraoptic nucleus in vivo. Tissues were then prepared for quantitative electron microscopic analysis of the total incidence of DCVs within supraoptic dendritic cross-sections, and of the incidence and distance (within a 500-nm margin) of each DCV to the dendritic plasma membrane. Salt loading per se did not alter the frequency distribution or average proportion of DCVs found in the 500-nm margin but significantly decreased the average incidence of DCVs per dendrite by 30% (P < 0.05). However, thapsigargin treatment resulted in a significant increase in the total incidence of DCVs within the 500-nm margins and a higher incidence of DCVs within the first 200 nm of the plasma membrane (P < 0.05), indicating that the thapsigargin-induced priming involves a relocation of DCVs closer to sites of secretion.
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PMID:Thapsigargin-induced mobilization of dendritic dense-cored vesicles in rat supraoptic neurons. 1514 25

The hypothalamo-neurohypophysial system (HNS), synthesizing arginine vasopressin (AVP) and oxytocin (OXT), is well known to show structural plasticity during chronic physiological stimulation such as salt loading and lactation. In the present study, we undertook in the HNS to study localization and activity-dependent changes in the expression of matrix-degrading enzymes such as tissue plasminogen activator (tPA) and matrix metalloprotease-3 (MMP-3). Double labeling confocal microscopy demonstrated that the immunoreactivity of tPA was localized at AVP-positive dendrites in the supraoptic nucleus (SON) and AVP-positive terminals in the neurohypophysis (NH). The immunoreactivity of tPA was also seen at astrocytic processes in the HNS. Likewise, the immunoreactivity of MMP-3 was observed at AVP-positive dendrites and terminals. High magnification observation further revealed punctate distribution of tPA and MMP-3 immunoreactivity at dendrites and terminals, suggesting that they are localized at neurosecretory granules. Salt loading, known as the chronic stimulation to cause the structural plasticity, increased protein and mRNA levels of tPA in the SON but reduced protein levels of it in the NH. The chronic stimulation also increased protein levels of urokinase plasminogen activator in the SON, but the stimulation did not change protein levels of MMP-3 in the SON and NH. Depolarizing agent KCl released tPA from isolated neurosecretosomes, and this depolarization-dependent release was abolished by verapamil, a Ca(2+) channel blocker. These results demonstrate that tPA and MMP-3 are localized mainly at dendrites and terminals of AVP-expressing magnocellular neurons and tPA is released in an activity-dependent manner, suggesting that matrix-degrading proteases are candidate molecules to be concerned with the structural plasticity in the HNS.
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PMID:Matrix-degrading enzymes tissue plasminogen activator and matrix metalloprotease-3 in the hypothalamo-neurohypophysial system. 1615 Apr 23

Salt loading reduces neuroendocrine responses to stressful stimuli. Noxious stimuli facilitate noradrenaline release in the hypothalamus and, as a result, activate oxytocin neurones. Here, we examined effects of salt loading upon plasma oxytocin concentrations and noradrenaline release in the hypothalamus after footshocks. Male rats were allowed to drink 2% NaCl for 7 days. Salt loading reduced the footshock-induced increase in plasma oxytocin concentrations and noradrenaline release in the supraoptic nucleus (SON). Acute administration of hypertonic saline also attenuated the footshock-induced noradrenaline increase in the supraoptic nucleus. In contrast, salt loading did not significantly change activation of A1 catecholaminergic neurones in the medulla oblongata, as measured by expression of Fos protein. These data suggest that salt loading presynaptically suppresses noradrenaline release in the hypothalamus and oxytocin release into the blood after footshocks.
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PMID:Salt loading reduces hypothalamic noradrenaline release after noxious stimuli. 1615 55


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