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)

In order to study the subcellular distribution of neurophysin in the rat with hypothalamic hereditary diabetes insipidus (DI), an immunoelectron microscopic localization of neurophysin was performed in the hypothalamo-neurohypophysial system of both homozygous and heterozygous DI rats. Whereas in control rats neurophysin was localized in the granules present in the secretory neurons, in the homozygous DI rats neurophysin was found in the granules and outside the granules in the perikarya and axons of neurons of both supraoptic and paraventricular nuclei. In the heterozygous DI rats findings similar to those observed in homozygous DI rats were observed, although in the posterior pituitary, the exgranular material appeared to be less abundant than in homozygous DI rats. These results clearly demonstrated that in hyperstimulated neurons neurophysin was distributed in both granular and extragranular compartments.
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PMID:Electron microscope immunohistochemical localization of neurophysin in the rat with hereditary diabetes insipidus. 82 4

In attempting to design an antagonist of the antidiuretic response to arginine-vasopressin (AVP) [1-deaminopenicillamine,4-valine,8-D-arginine]vasopressin (dPVDAVP) was synthesized by the solid-phase method and assayed for antidiuretic, vasopressor, and oxytocic activities. dPVDAVP has an antidiuretic potency of 123 +/- 22 units/mg, one-tenth that of its parent [deamino,4-valine,8-D-arginine]vasopressin (dVDAVP). Like dVDAVP its antidiuretic effect in conscious diabetes insipidus rats is greatly prolonged when compared to AVP. dPVDAVP causes a prolonged inhibition of vasopressor responses to AVP but not to norepinephrine or angiotensin II. It has an antivasopressor pA2 value of 7.82 +/- 0.05 when tested against AVP. Thus the penicillamine substitution at position 1 in dVDAVP increased its antivasopressor activity sixfold (dVDAVP has a pA2 value of 7.03 +/- 0.11). dPVDAVP is thus the most potent vasopressor antagonist yet reported. dPVDAVP was also found to be a potent inhibitor of the in vitro oxytocic response to oxytocin (pA2 value = 7.23 +/- 0.04). dPVDAVP with its potent and specific ability to antagonize the vasopressor effects of AVP should be a useful pharmacological tool with which to explore the possible participation of AVP's potent vasoconstrictor properties in cardiovascular regulation in physiological and pathological states.
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PMID:[1-deaminopenicillamine,4-valine]-8-D-arginine-vasopressin, a highly potent inhibitor of the vasopressor response to arginine-vasopressin. 92 26

Diabetes insipidus is an extremely rare condition complicating pregnancy. The deficiency in antidiuretic hormone production has led to the assumption that oxytocin synthesis may also be affected. For this reason spontaneous onset of labor in a number of previously reported cases has been considered as evidence against implicating oxytocin as a relevant factor in the evolution and maintenance of labor. For the first time, plasma oxytocin levels were determined in a patient with known idiopathic diabetes insipidus during pregnancy, labor, and postpartum, using radioimmunoassay. Oxytocin was not detectable in plasma before labor. There was however a surge of plasma oxytocin detected during labor and puerperium, a pattern somewhat similar to that seen in normal pregnancy. Our findings suggest that at least some patients with diabetes insipidus do secrete oxytocin and that the role of oxytocin, threfore, cannot be discounted in the labor process.
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PMID:Plasma oxytocin determinations in pregnancy with diabetes insipidus. 94 Jun 35

Observations on water and electrolyte metabolism after hypophysectomy or adrenalectomy, in male and female rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) are confirmed and extended. The diabetic (homozygous, DI) state relative to the non-diabetic (heterozygous, non-DI) state was characterized by (1) water intake of 55-120% body weight; (2) copious urine hypo-osmotic to plasma; (3) greater excretory rates of total solute, Na, Ca and Mg; (4) similar plasma composition except that in male DI rats, K concentration was less, and in female DI rats osmolarity was higher; (5) glomerular filtration rates (GFR) were similar with close correlations between: food and water intakes, water intake and output, urinary Na and K, Na and Cl, K and Cl, and Ca and Mg; (6) both female DI and non-DI rats had lower urinary Na:K ratios and lower plasma Na concentrations than males; (7) female DI rats excreted relatively larger amounts of K and Cl, and had higher plasma Ca concentrations than other groups. Hypophysectomized DI rats had decreased water intake and urine output, decreased solute excretion, decreased loss of osmotically free water, lower excretory rates of Na, K and Cl, and increased urinary osmolarity and K concentrations. Hypophysectomized non-DI rats had increased urinary excretory rates, decreased solute excretion (by 60-70%), decreased osmotically free water absorption, decreased urinary osmolarity, Na and K concentrations, and increased excretory rates of Ca and Mg. Hypophysectomized DI and non-DI rats had increased plasma osmolarity and Na concentration. Plasma renin activities (PRA) were higher in DI than in non-DI rats with female values lower than those of males; values for both sexes of DI and non-DI rats were reduced after hypophysectomy. Adrenalectomized DI rats had about a 50% reduction in water intake, urine output and free water clearance, increased urinary concentration of electrolytes and total solute by day 4 after operation; their Na balance (dietary:urine) did not change significantly in contrast to adrenalectomized non-DI rats in which a greater percentage of dietary Na appeared in the urine. GFR was similarly reduced in adrenalectomized DI and non-DI rats. Plasma osmolarity increased in adrenalectomized male DI, decreased in female DI and non-DI, and did not change in male non-DI rats. Plasma K concentrations increased after adrenalectomy in all groups, only non-DI rats had a significantly decreased plasma Na concentration. There was no sex difference in pituitary oxytocic activity but it was consistently reduced in DI rats; there was little change after adrenalectomy in male DI and non-DI rats; but there was an increase in DI and non-DI females. Pituitaries of DI rats had no measurable ADH activity (except the inherent activity of oxytocin). Pituitary ADH values for male and female non-DI rats were similar and were unaffected by adrenalectomy.
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PMID:Effects of adrenalectomy and hypophysectomy on water and electrolyte metabolism in male and female rats with inherited hypothalamic diabetes insipidus (Brattleboro strain). 101 Sep 70

The present paper deals with the development of an immunofluorescence procedure that allows specific localization of vasopressin and oxytocin in the hypothalamo-neurohypophyseal system(hnx) of the rat. Antibodies against arginine vasopressin (AVP), lysine-vasopressin (LVP) and oxytocin were raised by injecting these hormones that were covalently bound to thyroglobulin into rabbits. The vasopressin-immunized rabbits showed periods of diabetes insipidus, while histoloty of the "hns revealed an intact neurosecretory system with signs of increased endogenous hormone synthesis in the supraoptic nucleus and increased release in the neuro-hypophysis of some rabbits. The daily water intake of the oxytocin-immunized rabbits was similar to that of control rabbits. The development of antibodies against vasopressin as measured in the immunofluorescence procedure showed a course that was quite different from the curve of the titer as determined by radioimmunoassay (RIA). Also the specificity of the antibodies used in the immunofluorescence procedure was found to be quite different from their specificity in a RIA system. Potency and specificity of the antibodies have to be studied therefore within the immunofluorescence procedure itself. Using freshly frozen acetone-postfixed hypotalami or pituitaries, no sharp localization of immunofluorescence could be obtained in the HNS. Therefore prefixation was performed. Both, the type and the duration of prefixation revealed quite different results regarding the immunofluorescence in the neurosecretory cell boides in the hypotalamus and of their endings in the neurohypophysis. The best immunofluorescence results were obtained using 6 hours glyoxal-prefixation for the hypothalamus and 24 hours formalin-prefixation for the pituitary. The cross-reaction of the antibodies for oxytocin or vasopressin was tested on synthetic hormones that were bound to CNBR-activated agarose beads and mounted on glass sides. All anti-plasmas showed cross-reaction on beads containing the heterologou- antigen. The plasmas were purified by incubation with beads containing the heterologous hormone until the cross-reacting component had been removed. Using purified antibodies, the distribution of oxytocin and vasopressin cells within the HNS was investigated. More oxytocin containing cells were localized in the rostral part and more vasopressin in the caudal part of both, the supraoptic (SON) and paraventricular nucleus (PVN). Comparable percentages of oxytocin and vasopressin containing cells were found in the SON and PVN. The absolute amount of oxytocin containing cells was 2.5 times more in the SON than in the PVN, which seems to contradict the "classical" view that the PVN predominantly or entirely synthetizes oxytocin. In addition, fluorescence was found using antobodies against vasopressin in the suprachiasmatic nucleus in Wistar rats and heterozygous Brattleboro rats, but not in this nucleus of homozygous Brattleboros.
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PMID:Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. 110 Jul 84

The 3-layer immunoperoxidase-bridge technique was used to study the distribution of neurophysin and vasopressin in the neurosecretory neurons of rats homozygous and heterozygous for diabetes insipidus (Brattleboro strain). In the homozygous rats there was a marked hypertrophy of the hypothalamic magnocellular structures when stained either for neurosecretory material or neurophysin-like antigens. Neurophysin was present in both the paraventricular (PVN) and supraoptic nuclei (SON) of homozygous and heterozygous animals. Less than half of the cells in the PVN and SON were stained for neurophysin. This observation was less apparent when histochemical stains were used to visualize the distribution of neurosecretory material. Although it is generally considered that the homozygous Brattleboro rat does not synthesize vasopressin, a positive reaction was observed in the PVN and SON when anti-[8-lysine]-vasopressin serum was employed in the immunohistochemical procedure.
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PMID:Presence of neurophysin and vasopressin in the hypothalamic magnocellular nuclei of rats homozygous and heterozygous for diabetes insipidus (Brattleboro strain) as revealed by immunoperoxidase history. 112 31

The cellular distribution of neurophysin was examined in hypothalami and neural lobes of normal Long-Evans rats and Brattleboro rats deficient in vasopressin and a major neurophysin. Tissue sections were treated with antisera to bovine, human, and rat neurophysins, using immunoperoxidase bridge techniques. Antisera to oxytocin (OT) and vasopressin (VP) were applied to adjacent sections. Two distinct cell populations were discernible in both magnocellular nuclei on the basis of the intensity of cytoplasmic staining. About half of the magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of homozygous Brattleboro rats with diabetes insipidus (DI) were devoid of immunoreactive neurophysin, OT, and VP. These cells were presumably the defective counterparts of those neurons that produce VP and its associated neurophysin in normal and heterozygous Brattleboro rats. The cells in homozygous DI rats which were stained with immunoreaction products to NP and OT were more concentrated in the dorsal part of the SON and in the periphery of the PVN. Spatial segregation of different neurons was also seen in the neural lobe, where clusters of stained axons were surrounded by bundles of nerve fibers lacking immunoreactive material. In normal rats and heterozygotes nearly all magnocellular neurons reacted immunologically with antiserum to neurophysin but with different intensities, so that "dark" and "light" cells could be distinguished. The darker cells in heterozygous Brattleboro rats had the same pattern of distribution as cells which contained OT. In homozygous DI rats, only some of those cells which contained neurophysin and OT exhibited a positive reaction with antiserum to VP due to slight reactivity with OT. The results obtained in the homozygous Brattleboro rat would suggest that OT and VP and their associated neurophysins are produced in different neurons in both the SON and PVN. However, in normal rats and in heterozygous Brattleboro rats, VP appeared to be present in both OT-positive and OT-negative neurons suggesting that some cells may have the capacity to synthesize two hormones.
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PMID:The hypothalamic-neurohypophysial system of the rat: localization and quantitation of neurophysin by light microscopic immunocytochemistry in normal rats and in Brattleboro rats deficient in vasopressin and a neurophysin. 126 12

The homozygote Brattleboro rat exhibits a hereditary diabetes insipidus due to a deficiency of vasopressin, the antidiuretic hormone. It has previously been shown that in this animal a single nucleotide deletion in the provasopressin gene leads to a mutant precursor with a C-terminal amino acid sequence different from that of the wild-type. However the N-terminal region including the hormone moiety, the processing signal as well as the first two-thirds of the neurophysin is entirely preserved and absence of maturation has to be explained by an additional cause. We show here that the neurohypophysis of the homozygote Brattleboro rat, in contrast to the adenohypophysis, displays a significant decrease in the Lys-Arg processing endopeptidase activity when compared to the heterozygote or the wild-type Wistar. It is suggested that hypothalamic vasopressinergic neurons of the homozygote Brattleboro rat display a deficiency in the processing enzyme in contrast to the oxytocinergic neurons in which processing of prooxytocin is normal.
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PMID:Processing endopeptidase deficiency in neurohypophysial secretory granules of the diabetes insipidus (Brattleboro) rat. 129 35

In homozygous Brattleboro rats a frame-shift mutation in the vasopressin gene prevents secretion of vasopressin by magnocellular neurosecretory neurons and thus causes diabetes insipidus. Whereas most "vasopressin" neurons in Brattleboro homozygotes apparently lack vasopressin and its associated neurophysin and glycopeptide, some isolated cells overcome the mutation and "revert" to producing readily detectable amounts of vasopressin. We describe here two morphologically and immunocytochemically distinct subsets of such "revertant" cells. One subset contain, in their rough endoplasmic reticulum cisterns, electron-dense aggregates immunoreactive for vasopressin, for parts of oxytocin-neurophysin, and for CP14 (a peptide with a sequence deduced from the mutated precursor), but not for vasopressin-associated glycopeptide ("glycopeptide") or vasopressin-neurophysin. In Brattleboro heterozygotes, which have one mutant and one normal copy of the vasopressin gene, morphologically similar revertant cells exist; the aggregates in the rough endoplasmic reticulum of these cells do not immuno-label for CP14, but the cells do produce 160-nm neurosecretory granules immunoreactive for vasopressin, vasopressin-neurophysin and glycopeptide. In Brattleboro homozygotes, the second, more abundant subset of neurons which recover vasopressin immunoreactivity also express vasopressin-associated glycopeptide and CP14 but not oxytocin-neurophysin; both glycopeptide and CP14 are restricted to the rough endoplasmic reticulum but do not form aggregates. We conclude that two different somatic repairs of the Brattleboro mutation can occur. We propose that, in aggregate-containing neurons, exons B and C have been exchanged between the vasopressin and oxytocin genes; glycopeptide-immunoreactive neurons have either undergone mismatch repair or exchanged exon B.
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PMID:Immuno-electron microscopic evidence for two different types of partial somatic repair of the mutant Brattleboro vasopressin gene. 143 2

Two posterior pituitary hormones oxytocin and arginine-vasopressin control the important activities of water excretion, parturition and lactation. Both these hormones are synthesized as inactive precursors in the hypothalamus along with their carrier proteins neurophysin I and neurophysin II respectively and are activated upon transport to posterior pituitary. Human genes for both oxytocin-neurophysin I (OXT) and arginine-vasopressin-neurophysin II (ARVP) are cloned and found to be linked on chromosome 20 separated by approximately 12 kb of intergenic sequences. Though OXT is not yet associated with any disease, ARVP is linked to the autosomal dominant disease neurohypophyseal diabetes insipidus (AD-NDI). We have mapped regionally the OXT locus to chromosome 20p13 by both radioactive (ISH) and fluorescence in situ hybridization (FISH).
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PMID:The human gene for oxytocin-neurophysin I (OXT) is physically mapped to chromosome 20p13 by in situ hybridization. 148 3


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