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

Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be related to inhibition of sodium ingestion. The present studies evaluated this possibility by increasing brain OT concentrations both exogenously and endogenously in rats with hypovolemia produced by subcutaneous administration of polyethylene glycol (PEG) solution. Intracerebroventricular (i.c.v.) administration of OT completely abolished intake of 0.5 M NaCl in PEG-treated hypovolemic rats, but did not significantly affect PEG-stimulated water intakes. Endogenous OT secretion was stimulated by systemic treatment with naloxone, which has been shown to increase peripheral and central OT levels. In both one-bottle (0.5 M NaCl) and two-bottle (water and 0.5 M NaCl) drinking tests, intraperitoneal naloxone completely abolished sodium appetite in association with markedly increased pituitary secretion of OT. This inhibition of sodium appetite could be prevented by i.c.v. pretreatment with a specific OT-receptor antagonist, although the antagonist by itself did not affect PEG-stimulated sodium intake. These findings therefore support previous reports which have found that sodium appetite in rats is inhibited by treatments that elicit pituitary release of OT, and provide more direct evidence that brain OT is causally involved in the inhibition of sodium appetite stimulated by such treatments in rats.
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PMID:Central oxytocin mediates inhibition of sodium appetite by naloxone in hypovolemic rats. 140 80

The time course of acute changes in vasopressin (VP) and oxytocin (OT) mRNA size and level during dehydration has been studied in rats. Total RNA was extracted from samples of the supraoptic nucleus at various intervals after water deprivation, subjected to northern blotting, and probed with oligonucleotides specific for VP and OT mRNA. The VP and OT mRNA size, shown previously to reflect 3'-poly (A) tail length, was consistently increased 2 h after dehydration, prior to significant changes in plasma osmolality or haematocrit. Intraperitoneal administration of hypertonic saline resulted in a similarly rapid VP and OT mRNA size response, in some cases within 1 h of treatment. The effect of a discrete hypovolaemic stimulus was investigated with intraperitoneal injections of polyethylene glycol; again, the VP and OT mRNA size was rapidly increased. No significant changes in mRNA level were observed in any of the experimental groups. The results show that an increase in VP and OT mRNA poly(A) tail length forms an acute and general response to activation of the hypothalamo-neurohypophyseal system. The rapidity of the poly (A) tail response, which appears to be independent of physiological signalling mechanisms associated with increases in mRNA accumulation (observed after 2 days of dehydration), provides a paradigm for the investigation of novel modes of neuronal gene regulation.
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PMID:Rapid changes in poly (A) tail length of vasopressin and oxytocin mRNAs form a common early component of neurohypophyseal peptide gene activation following physiological stimulation. 167 37

Chemical and photoaffinity cross-linking experiments as well as ligand affinity blotting techniques were used to label the V1 vasopressin receptor. In order to determine the optimal reaction conditions, pig liver membranes were incubated with 5 nM [8-lysine]vasopressin (LVP) labeled with 125I and then cross-linked with the use of DMS (dimethyl suberimidate), EGS [ethylene glycol bis(succinimidyl succinate)] or HSAB (hydroxysuccinimidyl p-azidobenzoate) at different final concentrations. Consistently, EGS was found to label with high yield one band of Mr 60,000 in rat and pig liver membranes when used at a final concentration between 0.05 and 0.25 mM. The protein of Mr 60,000 is labeled in a concentration-dependent manner when pig liver membranes are incubated with increasing concentrations of 125I-LVP and then cross-linked with EGS. The label was displaced by increasing concentrations of unlabeled LVP or d(CH2)5 [Tyr2(Me),-Tyr9(NH2)]AVP (V1/V2 antagonist). A protein band of similar molecular mass was cross-linked with 125I-LVP in rat liver membranes. The reaction was specific since the incorporation of label into the protein of Mr 60,000 was inhibited by LVP, [8-arginine]vasopressin (AVP), the V1/V2-antagonist, and the specific V1-antagonist d(CH2)5 [Tyr2(Me)]AVP, only partially by [des-Gly9]AVP (V2-agonist) and by oxytocin, and not at all by angiotensin II. Incubation of nitrocellulose containing membrane proteins from pig liver with 125I-LVP showed the labeling of a band of Mr 58,000 that is inhibited by an excess of unlabeled LVP. This band of Mr 58,000 seems to correspond with the protein of Mr 60,000 revealed by the cross-linking experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of the V1 vasopressin receptor by chemical cross-linking and ligand affinity blotting. 183 97

An enriched preparation of neurosecretory granules from bovine pituitary neural lobes was used as a source of processing enzymes possibly involved in the cleavage of the proocytocin/neurophysin precursor. A synthetic eicosapeptide reproducing the entire (1-20) sequence of the NH2-terminal domain of the bovine ocytocin/neurophysin precursor was used as a substrate to monitor an endoprotease activity cleaving at the Lys11-Arg12 doublet. The 58-kDa endoprotease detected in the lysate of neurohypophyseal granules produced a single cleavage, after the doublet, at the Arg12-Ala13 peptide bond. This endoprotease with pHi 6.9 and 7.2 exhibits maximal activity at pH around neutrality (7.0) and was strongly inhibited by divalent cation chelating agents [ethylenediaminetetraacetic acid and ethylene glycol bis(beta-aminoethyl ether)-N,N,N',-N'-tetraacetic acid] and to some extent by p-(chloromercuri)benzoate and p-(chloromercuri)benzenesulfonic acid, while phenylmethanesulfonyl fluoride and pepstatin were not active. This endoprotease action was sensitive to any modification of the substrate at either basic amino acid of the doublet since replacement of either L-Lys11 or L-Arg12 by D-Lys or D-Arg and by L-Nle abolished the cleavage reaction. In contrast, reversal of the polarity of the doublet in [Arg11,Lys12]proocytocin/neurophysin(1-20) had no effect on the mode of endoproteolytic cleavage as well as modifications of Gly10 (replaced by Ala10). It is concluded that the selectivity of this endoprotease, which may be involved in the primary event occurring in proocytocin/neurophysin processing, is strictly dependent upon the integrity of the basic doublet but that other parameters determined by the amino acid sequence around this doublet may play an important role.
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PMID:Partial purification and functional properties of an endoprotease from bovine neurosecretory granules cleaving proocytocin/neurophysin peptides at the basic amino acid doublet. 282 69

Subcutaneous injection of polyethylene glycol (PEG) solution in rats produces exponential increases in secretion of arginine vasopressin (AVP) and oxytocin (OT) in proportion to the induced plasma volume deficits. Previously, we reported that acute water loads eliminated the neurohypophyseal hormone responses to hypovolemia, whereas hypertonic NaCl potentiated them. The present experiments indicated that AVP and OT secretion after PEG treatment were blunted by prior maintenance of rats on a sodium-deficient diet for 2 days. In contrast, plasma AVP and OT levels after PEG treatment were enhanced by prior adrenalectomy or ligation of the inferior vena cava or by concurrent administration of phentolamine in association with arterial hypotension. AVP and OT responses to hypovolemia were similarly potentiated in rats made uremic by bilateral nephrectomy or by puncturing their bladders. These results parallel previous findings that osmotic dilution and sodium deprivation each enhance the sodium appetite induced by PEG treatment in rats, whereas hyperosmolality, hypotension, and uremia each abolish it. Consequently, they support our previous hypothesis that sodium appetite is inversely related to the activity of hypothalamic oxytocinergic neurons.
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PMID:Neurohypophyseal secretion in hypovolemic rats: inverse relation to sodium appetite. 357 55

Overhydration inhibits release of vasopressin (VP) and oxytocin (OT) from the hypothalamo-neurohypophysial system during hypovolemia. We investigated whether opioid peptides mediate the inhibitory effect of water on secretion of these hormones. Conscious male rats were made hypovolemic by hemorrhage (HEM, 0.51 ml/min) of 20 and 35% of the blood volume or by injection of either subcutaneous polyethylene glycol (PEG, 20,000 mol wt, 35 ml/kg) or intraperitoneal histamine (HIS, 15 mg/kg, 1 ml/kg). Animals were intubated orally 1-4 min (HEM, HIS) or 6.75 h (PEG) later with or without administration of water (40 ml/kg). Four to seven min after intubation rats were injected with saline (1 ml/kg) or naloxone (2 or 5 mg/kg) and then decapitated 6-10 min later. Control animals were treated similarly but were not stimulated by hypovolemia. VP and OT were extracted from plasma and quantified by radioimmunoassay. Data were analyzed by analysis of variance. In HEM animals blood pressure fell and plasma osmolality increased, both of which correlated positively with the rise in plasma [VP] and [OT]. Overhydration lowered the plasma osmolality, attenuated the fall in blood pressure, and reduced [VP] and [OT] in plasma of HEM animals. The opiate receptor antagonist, naloxone, did not alter these changes in blood pressure or plasma osmolality, or the plasma [VP] after HEM in rats treated with or without water. Plasma [OT] was, however, increased by naloxone in both normally hydrated and overhydrated rats. Thus, regardless of the hydrational state of the animal, opioid peptides inhibited release of OT but not VP during hemorrhage. Data consistent with this interpretation were also obtained from rats made hypovolemic with PEG or HIS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of VP and OT release by water in hypovolemia is independent of opioid peptides. 360 88

The intestinal transport of vasopressin and oxytocin and their analogues 1-deamino-8-D-arginine vasopressin and 1-deamino-2-tyrosine(omicron-ethyl)-oxytocin was studied in everted segments of rat jejunum. The transported peptides were identified by specific RIA methods and by quantitative high pressure liquid chromatography. Transport rates were highest for 1-deamino-8-D-arginine vasopressin and lowest for vasopressin. No transport maximum and no competitive inhibition could be demonstrated. The distribution volume of the peptides in the intestinal mucosa was found to be smaller than that of polyethylene glycol. It is concluded that peptides of this size are transferred across the intestinal mucosa by passive processes.
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PMID:In vitro intestinal transport of vasopressin and its analogues. 371 36

Stretching of rat uterine strips induced phosphorylation of the 20,000-Da light chain of myosin to the same extent as was observed in strips contracted by carbachol or oxytocin. Stretching also reversed the partial dephosphorylation of light chain caused by treatment with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) for 1 min. However, complete dephosphorylation of the light chain with 50-min EGTA-treatment could not be reversed by stretch. When stretched uterine strips containing light chain with a phosphate content greater than 0.75 mol/mol were quick-released, active force developed. On the other hand, when the phosphate content of light chain was reduced to less than 0.25 mol/mol, quick-release of the stretched strips did not produce active force. It is shown that Ca2+ mobilized from intracellular sources is involved in stretch-induced phosphorylation. The data indicate that myosin light chain phosphorylation is a prerequisite for active force development in smooth muscle.
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PMID:Stretch-induced myosin light chain phosphorylation in rat uterus. 375 7

Adult male rats were injected subcutaneously with polyethylene glycol (PEG) solution, which causes hypovolemia by progressive isosmotic leaching of plasma fluid into a local edema. Plasma levels of arginine vasopressin (AVP) were found to increase exponentially in response to induced plasma volume deficits up to 40%. However, plasma AVP was reduced to basal levels when the rats were given either free access to drinking water or intragastric water loads that diluted plasma osmolality by only 3-6% despite continued hypovolemia. Administration of hypertonic NaCl stimulated AVP secretion as well. However, combined PEG and hypertonic NaCl treatments produced plasma AVP levels greater than expected from simple additivity of the independent effects of hypovolemia and osmotic concentration. Oxytocin secretion similarly was stimulated by treatment with either PEG solution or hypertonic NaCl, it was especially pronounced when both treatments were given, and it was inhibited by osmotic dilution despite marked hypovolemia. These effects are analogous to those seen when hypovolemia stimulates water intake but subsequent osmotic dilution inhibits thirst in PEG-treated rats.
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PMID:Interaction of osmotic and volume stimuli in regulation of neurohypophyseal secretion in rats. 394 41

Regulation of posterior pituitary secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats given electrolytic lesions of ventral nucleus medianus (vNM). As described previously, rats with such lesions were chronically hypernatremic and showed impaired drinking responses to an osmotic challenge. AVP secretion in response to osmotic stimuli also was significantly blunted, although sufficient increases in plasma AVP levels did occur, in association with an abnormally high range of plasma sodium concentrations, to allow urinary concentration comparable to control animals. These findings suggest that vNM lesions cause an upward resetting of the osmotic threshold for AVP secretion. In contrast, hypovolemia, produced by subcutaneous polyethylene glycol treatment, and hypotension, produced by phentolamine treatment, both evoked AVP responses in rats with vNM lesions that were equivalent to those seen in control animals. Plasma OT responses to osmotic and hemodynamic stimuli were analogous to the AVP responses. These findings reproduce the major clinical features observed in humans with the disorder of essential hypernatremia and by doing so support proposals that this disorder is caused by lesions in the vicinity of the anterior hypothalamus that result in selective destruction of afferent osmosensitive inputs to the neurohypophysis.
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PMID:Impaired secretion of vasopressin and oxytocin in rats after lesions of nucleus medianus. 407 88


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