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

The present investigations determined the effects of dietary sodium deprivation on the neurohypophysial secretion of arginine vasopressin (AVP) and oxytocin (OT) by rats in response to nonhypotensive hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. In rats fed either standard sodium-rich laboratory chow or sodium-deficient diet for 8 days, AVP secretion increased gradually in proportion to plasma volume deficits up to 22-28% while pituitary secretion of OT was not stimulated. However, when hypovolemia was more pronounced, secretion of both hormones was marked in rats fed standard chow, whereas rats fed sodium-deficient diet were significantly less responsive. These effects did not reflect a general insensitivity of the neurohypophysial system because sodium-deprived and chow-fed rats secreted AVP and OT equivalently in response to intravenous infusion of 1.5 M NaCl solution. Nor did they reflect a general insensitivity to hypovolemia because sodium-deprived rats drank substantial, above-normal volumes of water after colloid treatment. Instead, the results appear to reflect a specific inhibition of stimulatory baroreceptor inputs to AVP and OT neurons during dietary sodium deprivation in rats.
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PMID:Sodium deprivation blunts hypovolemia-induced pituitary secretion of vasopressin and oxytocin in rats. 797 62

To define changes in the magnocellular neuroendocrine system during lactation and pregnancy, we compared plasma levels of oxytocin (OT) and vasopressin (VP) after polyethylene glycol (PEG)-induced hypovolemia and cholecystokinin (CCK) stimulation. Conscious virgin, pregnant (day 20), and lactating (day 6) Sprague-Dawley rats were injected with either PEG (70-600 mg/ml; 35 or 70 ml/kg sc), CCK (100 micrograms/ml; 4 ml/kg ip), or vehicle and decapitated 4 h (PEG) or 5 min (CCK) later. Changes in thresholds for release of hormone and the responsiveness (slopes relating [hormone] to blood volume depletion or to plasma osmolality) of the OT and VP systems were determined using an iterative nonlinear threshold regression model. After PEG, plasma osmolality increased coincident with a decrease in blood volume, with both stimuli contributing to the rise in plasma VP and OT. Compared with virgin rats, neither the threshold nor the responsiveness of the VP system was altered by the combined stimulus, whereas the oxytocinergic system of pregnant rats was more responsive to osmotic component. Lactating rats, however, had a higher threshold for VP release and an apparent elevation of the OT threshold beyond 25% volume depletion. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT. Intraperitoneal CCK elevated plasma [OT] in each reproductive state, although the response in lactating animals was attenuated. In virgin and lactating rats, plasma levels of VP also increased slightly but significantly in response to CCK. During gestation when cardiovascular volume is expanded, both the VP and OT neuroendocrine systems were reset, enabling secretion of both hormones in response to hypovolemia with hypertonicity. During lactation, both neuroendocrine systems are reset such that greater changes in fluid balance are needed to stimulate hormone release. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT, indicative of preferential release of VP with less than a 5% (virgin, pregnant) or a 20% (lactating) loss in blood volume.
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PMID:Response of the magnocellular system in rats to hypovolemia and cholecystokinin during pregnancy and lactation. 818 79

Sodium chloride ingestion is stimulated during conditions of sodium deficiency to maintain body fluid and electrolyte balance. Recent studies have indicated that salt appetite in rats is often inversely related to peripheral and central secretion of the hormone oxytocin (OT). We studied the potential role of central OT on salt and water ingestion by treating rats intracerebroventricularly with OT conjugated to the A chain of the plant cytotoxin ricin (rAOT) to produce a chronic selective inactivation of brain cells containing OT-receptive elements. The rats treated with rAOT and control rats treated with the ricin A chain alone were given 5-hr two-bottle (water and 0.5 M NaCl) drinking tests 30 min after they were made hyperosmolar by injections of hypertonic (2M) mannitol solution, which elevated plasma osmolality but reduced plasma Na+ concentration. In the control rats only water intake was stimulated in response to the induced hyperosmolality, but in the rAOT-treated rats hypertonic mannitol caused a robust salt appetite as well as thirst. Analogous results were obtained in rats treated with two different OT-receptor antagonists prior to induction of hyperosmolality with mannitol. In contrast to these results, when hyperosmolality was induced by administration of equivalently hypertonic (1M) NaCl, which elevated both plasma osmolality and plasma Na+ concentration, only water intake but not salt intake was stimulated in both control and OT-receptor antagonist-treated rats. When salt appetite was stimulated by the physiological stimulus of polyethylene glycol-induced hypovolemia, hypertonic mannitol similarly inhibited salt ingestion in control animals but not in rAOT-treated rats, whereas hypertonic NaCl inhibited subsequent salt ingestion in both groups. These results suggest that salt appetite is regulated by both Na(+)- and osmolality-sensing mechanisms in rats. In addition, they indicate that central OT likely mediates a significant component of osmolality-related inhibition of salt appetite but does not appear to be essential for Na(+)-related inhibition of this important homeostatic behavior.
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PMID:Central oxytocin inhibition of salt appetite in rats: evidence for differential sensing of plasma sodium and osmolality. 823 2

To determine whether the effect of oxytocin (OT) on progesterone production in primate luteal tissue may be receptor-mediated, we used biochemical procedures to examine the CL of the baboon (Papio anubis) for the presence of OT receptors (OT-R). CL (n = 5) were obtained by luteectomy from the early (LH + 1-5 days), mid- (LH + 6-10 days), and late (LH + 10-15 days) luteal phases. Biopsies from the uterine fundus were also obtained at the same time. Total receptors were measured by incubating the membrane fractions (120,000 x g fraction) with increasing concentrations of [3H]oxytocin (0.08-1.6 nM) for 30 min at 22 degrees C with a protein concentration of 200 micrograms per tube. Nonspecific binding was evaluated by the addition of excess nonradioactive OT. The receptor-bound tritiated ligand was separated from the nonreceptor-bound ligand through use of polyethylene glycol. For the midluteal phase CL, the affinity Kd was 1.70 +/- 0.03 nmol/L and the mean receptor number (RT) was 122.6 +/- 8.3 fmol/mg protein. In comparison, myometrial tissue examined at the same phase of the cycle had a Kd of 1.3 +/- 0.1 nmol/L and an RT of 205.0 +/- 49.7 fmol/mg protein. Receptors were not detectable in the late luteal phase CL and were significantly lower in the early luteal phase CL (50.7 +/- 6.9 fmol/mg protein), with no difference in the Kd value. Competitive studies with structurally related and nonrelated peptides indicated the presence of specific receptors for OT in baboon CL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Baboon corpus luteum: presence of oxytocin receptors. 839 95

Ionic mechanisms responsible for histamine-induced prolonged depolarization in supraoptic nucleus neurons were investigated using whole-cell patch recordings in horizontally prepared brain slices from adult male rats. Bath application of histamine (1-10 microM) in control medium induced membrane depolarization in nine of 12 phasically firing, putative vasopressin cells, but not in continuous firing, putative oxytocin cells (none of five cells). Depolarization, usually accompanied by increased firing rate, started within 20 s after histamine reached the slices, lasting for 3-13 min, after which they repolarized, and this was repeatable upon washout. Chelation of intracellular Ca2+ with 11 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetate and perfusion of slices with Ca(2+)-free medium blocked neither histamine-induced membrane depolarizations nor increased firing rates in 24 of 30 cells recorded. Depolarizations were always associated with decreases in membrane conductance. Following treatment with promethazine (H1 receptor antagonist) in six cells excited previously by histamine, subsequent application induced neither membrane depolarization nor increased firing. H1 receptor agonists mimicked histamine-induced depolarization (four of six cells) but the H2 receptor agonist, dimaprit (10 microM), had no effect (all of nine cells). In medium containing 0 mM Ca2+, 2 mM Co2+ and 1-2 microM tetrodotoxin, with internal Ca2+ chelation, bath application of histamine induced an apparent inward current in 15 of 20 supraoptic neurons tested. The peak of inward current evoked by 1-10 microM histamine at holding potentials around -50 mV varied from 10 to 50 pA (27.3 +/- 0.3 pA, mean +/- S.E.M.). Ramp voltage tests revealed that this inward current decreased as membrane potential was hyperpolarized and had a reversal potential of -90.1 +/- 3.8 mV (n = 10). Subtraction of current obtained before from that during histamine application revealed a current that was linear against membrane potential. Increasing external K+ concentration or introduction of K+ channel blockers in the medium attenuated or abolished histamine-induced inward current at membrane potentials close to -50 mV. When external Cl- concentration was reduced, histamine-induced inward current was still seen in five of seven supraoptic cells tested. Neither inward current nor change in conductance was observed following bath application of histamine in 11 of 12 neurons recorded using patch pipettes containing guanosine 5'-O-(2-thiodiphosphate), and in seven of eight neurons using pipettes containing guanosine 5'-O-(3-thiotriphosphate). These results suggest that histamine depolarizes supraoptic neurons, at least in part, by inhibiting a K+ leakage current mediated by H1 receptors linked to GTP-binding proteins and Ca(2+)-independent pathways. This study provides initial evidence for the second messengers regulating K+ leakage current.
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PMID:Histamine-induced prolonged depolarization in rat supraoptic neurons: G-protein-mediated, Ca(2+)-independent suppression of K+ leakage conductance. 884 19

Using as models the neurohypophyseal nonapeptide hormone oxytocin and its analogue deaminooxytocin, several directed routes to formation of sulfur-sulfur bridges have been developed and evaluated. The linear sequences (through common octapeptide-resin intermediates) were assembled smoothly on tris(alkoxy)benzylamide (PAL) poly(ethylene glycol)-polystyrene (PEG-PS) graft supports, using stepwise Fmoc solid-phase chemistry. Side-chain protection of beta-mercaptopropionic acid (Mpa) and/or cysteine (Cys) was provided by S-2,4,6-trimethoxybenzyl (Tmob), S-acetamidomethyl (Acm), and/or a series of sulfenyl thiocarbonate and carbamoylsulfenyl protecting/activating groups: S-(methoxycarbonyl)sulfenyl (Scm), S-(methoxycarbonyl)disulfanyl (Sscm), S-(N-methyl-N-phenylcarbamoyl)sulfenyl (Snm), and S-(N-methyl-N-phenylcarbamoyl)disulfanyl (Ssnm). Thiolytic displacement of S-Snm (preferred) or S-Scm provided intramolecular cyclized peptide disulfides, and homologation of the chemistry with S-Ssnm (again preferred) and S-Sscm provided the corresponding trisulfides along with smaller amounts of disulfides and tetrasulfides. These chemistries could be implemented both in solution and in solid-phase modes. Various parameters were studied systematically and optimized, and the novel trisulfides of oxytocin and deaminooxytocin were synthesized and purified to homogeneity. The trisulfide compounds were evaluated in three assays: uterotonic in vitro, uterotonic in vivo, and pressor tests, and they showed substantial potencies, ranging from 5% to 40% of the parent (disulfide) activities, as well as protracted actions. The affinities of the peptide trisulfides to uterine membrane receptors were only 3.3-3.6-fold lower than those of the parent disulfides. Possible explanations of the biological results are discussed.
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PMID:Synthesis and pharmacology of novel analogues of oxytocin and deaminooxytocin: directed methods for the construction of disulfide and trisulfide bridges in peptides. 908 75

Enzymatic cleavage of some peptide hormones, neurotransmitters and neuromodulators could be implicated in the regulation of extra- and intracellular fluid volume and osmolality. Prolyl endopeptidase is known to hydrolyze several peptides, which act on hydromineral balance, such as angiotensins, bradykinin, vasopressin, oxytocin, thyrotropin-releasing hormone, neurotensin and opioids. In this work, we analyzed the effects of certain volume and/or osmotic changes in the activity of the soluble and membrane-bound prolyl endopeptidase in several brain areas, heart, lungs, kidney and adrenal and pituitary glands of the rat. Soluble prolyl endopeptidase activity was higher in the renal cortex of the chronic salt-loaded rats than in the control rats. In the water-deprived and polyethylene glycol-treated rats, heart particulate prolyl endopeptidase was lower than in the control rats. Particulate prolyl endopeptidase was also lower in the adrenal gland of the acute salt-loaded rats and in the brain cortex of the water-loaded rats than in the control rats. Data suggest that tissue-dependent peptide hydrolysis evoked by prolyl endopeptidase activity is involved in the water-electrolyte homeostasis.
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PMID:Effects of hydrosaline treatments on prolyl endopeptidase activity in rat tissues. 1149 89

To date, glucagon-like peptide 1(7-36) amide (tGLP-1) has been found to affect the neurohypophysial and cardiovascular functions in normotensive and normovolaemic rats. The aim of the present study was to investigate possible effects of tGLP-1 on the mean arterial blood pressure and the release of vasopressin and oxytocin under conditions of blood volume depletion in the rat. In the first series of experiments, the animals were injected i.p. with either 0.15 M saline or 30% polyethylene glycol (PEG). PEG caused an 18% reduction of blood volume 1 h after injection. No significant changes in the mean arterial blood pressure were found in either normo- or hypovolaemic rats during the experiment. tGLP-1 injected i.c.v. at a dose of 1 microg/5 microl 1 h after the i.p. injection increased similarly the arterial blood pressure in normo- and hypovolaemic rats. The plasma vasopressin/oxytocin concentrations were markedly elevated in hypovolaemic animals and tGLP-1 further augmented the release of both hormones. In the second study, hypovolaemia was induced by double blood withdrawal. The haemorrhage resulted in a marked decrease of the mean arterial blood pressure and in the elevated plasma vasopressin/oxytocin concentrations. tGLP-1 injected immediately after the second blood withdrawal increased the arterial blood pressure. In parallel, tGLP-1 enhanced significantly vasopressin and oxytocin secretion when compared with haemorrhaged, saline-injected rats. The results of this study indicate that tGLP-1 may affect the arterial blood pressure and the secretion of neurohypophysial hormones under pathological conditions brought about by blood volume depletion.
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PMID:Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and cardiovascular functions under hypo- or normotensive hypovolaemia in the rat. 1183 48

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

Medullary catecholamine and hypothalamic neurosecretory oxytocin cells are activated by hypotension, but previous studies have provided uncertain outcomes concerning their ability to respond to a purely hypovolaemic stimulus. In the present study, injections of PEG/water and pentolinium were used to elicit non-hypotensive, isosmotic hypovolaemia and isovolaemic, isosmotic hypotension, respectively, in conscious rats. Animals were sacrificed 2 h after treatment. Immunolabelling for Fos, tyrosine hydroxylase and oxytocin established that these two stimuli activate almost identical populations of catecholamine neurons in the ventrolateral and dorsomedial medulla, and very similar populations of oxytocin cells in the supraoptic and paraventricular nuclei of the hypothalamus.
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PMID:Catecholamine and oxytocin cells respond to hypovolaemia as well as hypotension. 1296 Jul 71


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