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)

Familial neurohypophyseal diabetes insipidus in humans is a rare disease transmitted as an autosomal dominant trait. Affected individuals have very low or undetectable levels of circulating vasopressin and suffer from polydipsia and polyuria. An obvious candidate gene for the disease is the vasopressin-neurophysin (AVP-NP) precursor gene on human chromosome 20. The 2 kb gene with three exons encodes a composite precursor protein consisting of the neuropeptide vasopressin and two associated proteins, neurophysin and a glycopeptide. Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members. Comparison of the nucleotide sequences shows a G----T transversion within the neurophysin-encoding exon B. This missense mutation converts a highly conserved glycine (Gly17 of neurophysin) to a valine residue. RFLP analysis of six related family members indicates cosegregation of the mutant allele with the DI phenotype. The mutation is not present in 96 chromosomes of an unrelated control group. These data suggest that a single amino acid exchange within a highly conserved domain of the human vasopressin-associated neurophysin is the primary cause of one form of ADNDI.
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PMID:A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus. 174 Jan 4

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
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PMID:Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions. 268

There is considerable disagreement in the literature on changes in the hypothalamo-neurohypophyseal system (HNS) with aging: some reports support HNS degeneration, whereas others claim an activation of this system in senescence. In order to study age-related changes in vasopressin (VP) and oxytocin (OT) excretion in relation to water metabolism, six young (4 months) and 12 aged (34 months) male Brown-Norway rats were placed in metabolism cages. Since plasma testosterone levels have been reported to affect HNS activity and to decline progressively with age, half of the aged animals were given subcutaneous testosterone implants. Urine volume and water intake were significantly increased in aged animals, while urine osmolality was significantly reduced. These changes could not be attributed to diminished VP secretion, since 24-h urinary excretion of this peptide was elevated in the aged animals. In addition, 24-h OT excretion was elevated in the aged animals, indicating an overall activation of the HNS in senescence. VP excretion was significantly correlated with urine osmolality, urine volume and urinary VP concentration. No significant differences were observed between testosterone- and sham-implanted aged rats. It is concluded that the moderate polyuria/polydipsia in the senescent Brown-Norway rat is probably due to renal changes and is accompanied by a compensatory rise in both VP and OT secretion. Testosterone does not affect these changes.
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PMID:Vasopressin and oxytocin excretion in the Brown-Norway rat in relation to aging, water metabolism and testosterone. 321 21

These experiments were designed to characterize the nature and extent of diabetes insipidus present in a new model of genetic vasopressin (VP) deficiency, the Roman high avoidance rat homozygous for diabetes insipidus (RHA: di/di strain). The new strain was developed from an initial cross between Long-Evans derived Brattleboro (LE:di/di) rats and normal Roman high avoidance (RHA: +/+) rats, and has been bred to be congenic with the parent RHA: +/+ strain. RHA: di/di rats exhibited polydipsia, excreted dilute urine, and exhibited elevated plasma osmolality. RHA: di/di rats shows a similar urinary response to dehydration as LE: di/di rats. VP was undetectable by radioimmunoassay in the serum, brain, and neurohypophysis of RHA: di/di rats. VP-neurophysin containing cells were not observed in the brains of RHA: di/di rats upon immunocytochemical analysis. Thus, the new RHA: di/di strain exhibits essentially the same profile of diabetes insipidus as the LE: di/di rat. The congenic relationship between RHA: di/di and RHA: +/+ rats makes the RHA: di/di rat a useful model under circumstances where genetic variables unrelated to VP deficiency may confound the interpretation of data.
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PMID:Characterization of a new rodent model of diabetes insipidus: the Roman high avoidance rat homozygous for diabetes insipidus. 373 82

In the late 1950s the inbred polydipsic mice, STR/N, was discovered. The early studies indicated that the extreme polydipsia was not due to a lack of vasopressin but probably due to innate thirst of unknown origin. Because the recent investigation has revealed the presence of some functional abnormality in the brain of the STR/N mouse, we now investigated, using immunohistochemical techniques, distribution of vasopressin (AVP)- and oxytocin (OXT)-containing neurones in the hypothalamus of polydipsic strain of mouse and compared with that of the control. The pattern of distribution of AVP- and OXT-immunoreactive neurones in the paraventricular (PV), supraoptic (SO), and suprachiasmatic nuclei (SCN) of the STR/N polydipsic mouse was similar to that of the control, but the number of AVP-immunoreactive neurones was more numerous in the PVN and SON and less in the SCN in the polydipsic mouse than in the control. In addition, a discrete group of AVP- and OXT-containing neurones that was not clearly seen in the control was discovered in the STR/N. These results implicate that abnormal distribution in the brain AVP and OXT contribute to the mechanism responsible for the polydipsia shown by the strain STR/N.
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PMID:Vasopressin- and oxytocin-immunoreactive hypothalamic neurones of inbred polydipsic mice. 849 Jul 39

We investigated the expression of neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and supraoptic nuclei (SON) of rats with inherited diabetes insipidus (DI), using in situ hybridization histochemistry. The DI rats showed hypo-osmotic polyuria and polydipsia with arginine vasopressin (AVP) deficiency. The expression of nNOS gene in the PVN and SON in homozygous (di/di) rats was significantly increased in comparison to normal Wistar and heterozygous (di/+) rats. nNOS gene-expressing cells were distributed throughout the PVN and SON, including the divisions of AVP and oxytocin gene expressing cells in di/di rats. These results suggest that the expression of nNOS gene is upregulated in the magnocellular neurons in the PVN and SON of inherited DI rats.
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PMID:Upregulation of neuronal NOS mRNA in the PVN and SON of inherited diabetes insipidus rats. 946 64

Vasopressin (AVP), angiotensin II (Ang II) and oxytocin (OT) receptors were mapped in the brain of inbred polydipsic mice of the STR/N strain by quantitative in vitro autoradiography and receptor binding levels, compared with those found in control non-polydipsic mice of the ICR strain. A remarkable difference was evidenced in the thalamic paraventricular nucleus where AVP receptor binding was 7- to 10-fold higher in polydipsic mice than in control mice. Another disparity was observed in the hypothalamic paraventricular nucleus, which contained AVP binding sites in the control mice, but was unlabelled in the polydipsic animals. Ang II receptor binding was reduced in the hypothalamic paraventricular nucleus of the polydipsic mice, whereas it was abundant in the brainstem region, encompassing area postrema and the nucleus of the solitary tract. The distribution and amount of OT receptor binding were similar in the polydipsic and control mice. Strain-related differences of AVP and Ang II receptor binding were observed both in male and female animals. A sex-related difference was seen only for OT receptor binding in the hypothalamic ventromedial nucleus, where labelling was less intense in males than in females of both strains. Altogether, our results support the view that central AVP and Ang II systems are involved in the mechanisms responsible for polydipsia in STR/N mice.
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PMID:Up-regulation of vasopressin and angiotensin II receptors in the thalamus and brainstem of inbred polydipsic mice. 1186 39

In the present study, we investigated the role of vasopressin in the development of quinpirole-induced hyperdipsia in the rat. We report that: (1), an acute intraperitoneal (i.p.) injection of 0.56 mg/kg of quinpirole increased plasma vasopressin (radioimmunoassay) at 15 min but not at 30 or 120 min; (2), nine daily injections of quinpirole (0.56 mg/kg, i.p.) progressively increased water intake and diuresis for a period of several hours after each treatment; (3), quinpirole hyperdipsia was associated with apparently normal levels of vasopressin (which might be considered inappropriately high in the presence of excessive drinking); (4), quinpirole reduced vasopressin and oxytocin, but not angiotensin, immunoreactivity in the supraoptic nucleus. These findings suggest that quinpirole hyperdipsia is a sound animal model of psychotic polydipsia.
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PMID:Dissociation in the effects of the D2/D3 dopaminergic agonist quinpirole on drinking and on vasopressin levels in the rat. 1204 26

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the arginine vasopressin (AVP) precursor. The pathogenesis of FNDI is proposed to involve mutant protein-induced loss of AVP-producing neurons. We established murine knock-in models of two different naturally occurring human mutations that cause FNDI. A mutation in the AVP signal sequence [A(-1)T] is associated with a relatively mild phenotype or delayed presentation in humans. This mutation caused no apparent phenotype in mice. In contrast, heterozygous mice expressing a mutation that truncates the AVP precursor (C67X) exhibited polyuria and polydipsia by 2 months of age and these features of DI progressively worsened with age. Studies of the paraventricular and supraoptic nuclei revealed induction of the chaperone protein BiP and progressive loss of AVP-producing neurons relative to oxytocin-producing neurons. In addition, Avp gene products were not detected in the neuronal projections, suggesting retention of WT and mutant AVP precursors within the cell bodies. In summary, this murine model of FNDI recapitulates many features of the human disorder and demonstrates that expression of the mutant AVP precursor leads to progressive neuronal cell loss.
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PMID:A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons. 1466 Jul 40

Hyponatremia can be classified as acute or chronic depending on its duration, and treatment options are tailored to this classification. However, it is sometimes difficult to differentiate acute from chronic hyponatremia in the Emergency Department (ED). The objective of this study was to identify characteristics to help diagnose and manage acute hyponatremia in the ED. Patients with acute hyponatremia in the ED were enrolled from a retrospective 2-year chart review. Eleven patients (0.8%) were identified with acute hyponatremia out of a total of 1321 hyponatremic patients. There were nine women and two men. The mean age was 48.9 years. The mean sodium (Na(+)) level was 115+/-4 mmol/L. Accompanying biochemical abnormalities included hypouricemia and hypouremia with increased fractional excretions of uric acid (UA) and urea. The estimated amount of water intake ranged from 2.5 to 10 liters (mean, 5.1+/-2.3 liters) during the day before ED presentation. All patients were treated with hypertonic saline and furosemide at a correction rate of 1.6+/-0.5 mmol/L/h. No patients had neurological sequelae after treatment. The causes of acute hyponatremia included induction of abortion with oxytocin (n=1), primary polydipsia on neuroleptic agents (n=2), polyethylene glycol (PEG) preparation for colonoscopy (n=1), diuretic therapy for hypertension (n=4), ecstasy use (n=1), and weight-reducing herbal teas (n=2). We conclude that in the right clinical setting, high free water intake and low serum urea and UA favor acute hyponatremia. A detailed drug history may be helpful in the differential diagnosis of acute hyponatremia.
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PMID:Biochemical and etiological characteristics of acute hyponatremia in the emergency department. 1624 91


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