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 present study examines the relative levels of vasopressin (AVP) mRNA within the paraventricular (PVN), supraoptic (SON), and suprachiasmatic (SCN) nuclei of the rat hypothalamus, and details the rates at which these levels change over the course of a 6 d salt-loading regimen. The quantitation of vasopressin mRNA was achieved by using three different procedures: (1) cell-free translation in rabbit reticulocyte lysate or (2) Northern analysis of poly(A)RNAs isolated from micro-punch dissected SON, PVN, and SCN, and (3) in situ hybridization histochemistry. The former involved the quantitative immunoprecipitation of the neurophysin precursors containing arginine8-vasopressin (AVP) or oxytocin, and the latter two techniques employed a radiolabeled synthetic oligodeoxynucleotide complementary to the 3' region of the AVP mRNA. Both the cell-free studies and the Northern gel analyses detected a sevenfold increase of AVP mRNA in the SON, a fivefold increase in the PVN, and no significant change in the SCN following 6 d of salt-loading. After the initiation of salt-drinking, these increases were shown to occur between 24 and 48 hr in the SON and between 48 and 72 hr in the PVN. The in situ hybridization studies revealed the anatomically correct hybridization of either 32P- or 3H-labeled AVP oligonucleotide to magnocellular perikarya within both the SON and PVN. Autoradiographic grains could be shown to be confined to the cytoplasm of these cells, and could be co-localized with immunoreactivity directed against the carboxy terminus of the AVP percursor. Comparison of x-ray level autoradiograms of control and 6 day salt-loaded SON revealed up to a sevenfold increase in specific signal in the salt-loaded sections. It is concluded that the response of AVP mRNA to osmotic stimuli in the three hypothalamic nuclei is heterogeneous, and that this heterogeneity can be explained by separating AVP neurons into two systems: one responsible for eliciting the antidiuretic actions of AVP via plasma AVP levels, and the other involved in CNS activities not directly involved with antidiuresis.
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PMID:Vasopressin mRNA regulation in individual hypothalamic nuclei: a northern and in situ hybridization analysis. 371 4

We examined the renal effects of synthetic oxytocin (OT) in the presence and absence of vasopressin in conscious euvolemic rats. Both sexes of the Long-Evans (LE) and Brattleboro homozygous (DI) strains were used. OT infused intravenously at 0.25 and 2.5 ng X min-1 X 100 g body wt (BW)-1 resulted, respectively, in plasma concentrations of 30 +/- 6 and 265 +/- 88 pg/ml in LE rats and 46 +/- 5 and 327 +/- 29 pg/ml in DI rats. Glomerular filtration rate (GFR) was augmented most consistently by the larger dose of hormone in LE rats (P less than 0.05), whereas the low infusion rate of OT enhanced GFR in DI rats (P less than 0.01). Effective renal plasma flow was not changed significantly. OT (both doses) increased the fractional excretion of sodium two- to threefold in each strain of animal (all at least P less than 0.05 from control), whereas the fractional excretion of potassium was largely unaffected. In LE rats, a diuresis was observed with either infusion rate of hormone, accompanied by a rise in osmolar clearance (COsm). In contrast, there was no change of urine flow with the low dose of OT in DI rats, because COsm increased and the clearance of free water (CH2O) decreased proportionately. The higher infusion rate of OT promoted antidiuresis in DI rats, with negative CH2O and little change in COsm. We conclude that oxytocin enhances GFR and is natriuretic regardless of the presence or absence of endogenous vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of oxytocin on renal hemodynamics and electrolyte and water excretion. 374 Feb 76

Studies of prostaglandins (PGs) used for term labor induction are reviewed, and aside from a slight tendency toward developing hypertonus with PGF2 alpha, evidence suggests that prostaglandins for labor induction, while no better than oxytocin, are equally efficacious. After the discovery of PGF2 alpha in the decidua of term pregnant uterus, impetus for research was found. Research first tended to record uterine activity, and next dose-response studies were performed. For labor induction studies, a double-blind study of 300 patients found a comparative advantage in efficacy of PGE2 over PGF2 alpha combined with oxytocin. Other double-blind studies reported an apparent synergism between oxytocin and PGE2 or, on the contrary, reported no difference in efficacy. Anderson's protocol design, using a double-blind protocol with Bishop score-classified patients before induction, has been modified but remains the basis of most protocols. Only in special situations has PGF2 alpha been found more efficacious than oxytocin; such situations are missed abortion, intrauterine death, molar gestations, and anencephalic pregnancy. 1 researcher suggests PGF2 alpha is indicated in patients with very low Bishop scores. Studies on the safety of prostaglandins for labor induction, for both child and mother, have generally concluded that if uterine hyperstimulation is avoided, there will be no serious sequelae. Hypertonus can be avoided by using step-wise dose increases based on labor progression, rather than fixed dose amounts. Also, in terms of safety, there is a possible advantage of PGF2 alpha over oxytocin in the area of antidiuresis, since 1 study has shown that PGF2 alpha has no antidiuretic effect.
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PMID:Induction of term labor with intravenous PGF2 alpha: a review. 478 20

Water diuresis was induced in six patients in mid-pregnancy. Three were then given oxytocin and the remainder prostaglandin F(2)alpha (PGF(2)alpha), both drugs being infused intravenously in doses used to induce labour at term. Pronounced antidiuresis occurred with oxytocin, whereas PGF(2)alpha showed no such effect. The probable absence of any risk of water intoxication when using PGF(2)alpha in inducing labour may be of particular value when maternal pre-eclampsia or renal disease is present.
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PMID:Absence of antidiuresis during administration of prostaglandin F2 alpha. 544 May 98

This chapter has reviewed briefly the neuroanatomy relevant to the synthesis and release of AVP and OXT. Osmoregulation and baroregulation of AVP secretion has been discussed in detail, emphasizing the importance of osmotic control under normal physiological conditions. The remainder of the text has covered the two major pathophysiological disturbances of AVP secretion. In considering diabetes insipidus a pragmatic approach has been taken in the differentiation of the causes of polyuria and its treatment. A similar approach has been applied to the syndrome of inappropriate antidiuresis. Brief mention was made of the function of OXT.
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PMID:Posterior pituitary function in health and disease. 636 55

Magnocellular neurons in the supraoptic and paraventricular nuclei synthesize and release vasopressin and oxytocin in response to dehydration. Pinealectomy has been observed to decrease the distribution in the supraoptic nuclei of thiamine diphosphate-phosphohydrolase, an enzyme specific for the Golgi apparatus that correlates positively with neurosecretory activity. Based upon these studies we postulated that pinealectomy would alter the concentration of neurohypohysial hormones in plasma elevated by 48 hr of water deprivation. In addition, we investigated the possibility that pinealectomy would affect vasopressin concentration in another circumventricular organ, the subfornical organ (SFO) and in a adjacent fiber tract of the limbic system, the hippocampal commissure-fornix (HC-F). Adult, male, Sprague-Dawley rats exposed to a 12 hr light/dark cycle were either unoperated (controls; C), sham-operated (Sham; S) or pinealectomized (PX) three weeks prior to testing. Food and water consumption and urinary excretion of Na and K were measured for 7 days. On the fifth day, half of the animals in each treatment group (C, S, PX) were deprived of water for 48 hr. Animals were decapitated on day 8. Vasopressin and oxytocin in plasma were extracted using bentonite and acetone-ether, respectively, then quantified by radioimmunoassay. The SFO and HC-F were microdissected from each brain. Like tissues from 4 rats were pooled, homogenized in 0.1 N HCl, and centrifuged. The supernatant was neutralized and vasopressin was quantified by radioimmunoassay. Dehydration resulted in antidiuresis, increased urine concentrations of Na and K, a decreased ratio of Na:K in urine, and reduced food consumption of similar magnitudes in all groups (C, S, PX; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of pinealectomy on neurohypophysial hormones in the SFO and plasma of dehydrated rats exposed to 12 hours of light. 666 81

Oxytocin administration in rat infused with hypotonic saline is associated with a saliuresis and altered renal water excretion. The role of vasopressin in determining the pattern of oxytocin-induced changes in urine flow was investigated in Long Evans and vasopressin-deficient Brattleboro rats, which exhibit contrasting diuretic and antidiuretic responses to oxytocin. Ethanol anaesthesia and water loading in Long Evans suppressed plasma vasopressin levels and was associated with an antidiuretic response to oxytocin. Vasopressin administration in the Brattleboro rat reversed the oxytocin-induced antidiuresis normally observed in vasopressin deficiency. These results taken with previous observations, have been interpreted as indicative that oxytocin acts as a weak agonist at the renal vasopressin receptor. When plasma vasopressin is suppressed or absent oxytocin acts as a weak antidiuretic agent, but in the presence of higher vasopressin levels a diuretic response to oxytocin is seen which follows displacement of vasopressin, the more potent antidiuretic agent, from the renal receptor.
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PMID:The influence of vasopressin on oxytocin-induced changes in urine flow in the male rat. 711 93

A new extremely sensitive radioimmunoassay to measure plasma AVP has been developed. Antiserum to AVP of high affinity (Keq = 1.1 X 10(12) 1/mol), raised in rabbits, showed little cross-reaction with related analogues (LVP less than 0.03%, AVT, DDAVP, OXT less than 0.01). The specific activity of 125I-AVP (chloramine T method) was 1400-1750 Ci/mmol. The limit of detection of plasma AVP, after extraction of 2 ml plasma with Florisil, was 0.3 pmol/1. Coefficient of variations of plasma control (2 pmo1/1) were 9.7% (intraassay) and 15.3% (inter-assay), n = 15. Osmotic stimulation by hypertonic saline infusion caused a linear response in plasma AVP in normal subjects, but plasma AVP remained undetectable in patients with cranial diabetes insipidus. Suppression of AVP secretion by a standard oral water load and by alcohol and fluid in volunteers produced low or undetectable values of plasma AVP. In a patient with the syndrome of inappropriate antidiuresis, plasma AVP concentration was grossly elevated.
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PMID:A new sensitive radioimmunoassay for plasma arginine vasopressin. 716 99

Arginine vasopressin modulates the release of adrenocorticotropic hormone, beta-endorphin, and prolactin from the anterior pituitary. Release is mediated by the V1b receptor through the mobilization of intracellular Ca2+ by phosphatidylinositol hydrolysis. In contrast to its well characterized peripheral actions, such as antidiuresis, contraction of vascular smooth muscle, and stimulation of hepatic glycogenolysis, the exact site and mechanism of vasopressin action in the pituitary remain unclear. This is largely due to a lack of information on the molecular identity and exact localization of the V1b receptor. This lack prompted us to try to isolate this receptor subtype. Here we report the molecular cloning and functional expression of a complementary DNA encoding the human V1b receptor. The deduced 424-amino acid sequence of the receptor has highest overall homology with the V1a, V2, and oxytocin receptors, with homologies of 45, 39, and 45%, respectively. The receptor expressed in COS-1 cells has a single binding site for arginine vasopressin with a Kd of 0.17 +/- 0.04 nM. It binds various agonists and antagonists of vasopressin with affinities distinct from those of V1a and V2 receptors but consistent with those anticipated for the V1b receptor on the basis of the pharmacological studies. Furthermore, arginine vasopressin evoked calcium-dependent chloride current in Xenopus oocytes transfected with the receptor, which was not affected by a V1a/V2 antagonist. In contrast, the current evoked in oocytes transfected with V1a receptor was abolished by the antagonist. Northern blot analysis revealed that the receptor expression is restricted to the pituitary. These data clearly indicate that the cloned cDNA encodes the V1b receptor.
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PMID:Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor. 792 52

The V2 vasopressin renal receptor (V2R), which controls antidiuresis in mammals, is a member of the large family of heptahelical transmembrane (7TM) G protein-coupled receptors (GPCRs). Using the automated GPCR modeling facility available via Internet (http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.+ ++html) for construction of the 7TM domain in accord with the bovine rhodopsin (RD) footprint, and the SYBYL software for addition of the intra- and extracellular domains, the human V2R was modeled. The structure was further refined and its conformational variability tested by the use of a version of the Constrained Simulated Annealing (CSA) protocol developed in this laboratory. An inspection of the resulting structure reveals that the V2R (likewise any GPCR modeled this way) is much thicker and accordingly forms a more spacious TM cavity than most of the hitherto modeled GPCR constructs do, typically based on the structure of bacteriorhodopsin (BRD). Moreover, in this model the 7TM helices are arranged differently than they are in any BRD-based model. Thus, the topology and geometry of the TM cavity, potentially capable of receiving ligands, is in this model quite different than it is in the earlier models. In the subsequent step, two ligands, the native [arginine8]vasopressin (AVP) and the selective agonist [D-arginine8]vasopressin (DAVP) were inserted, each in two topologically non-equivalent ways, into the TM cavity and the resulting structures were equilibrated and their conformational variabilities tested using CSA as above. The best docking was selected and justified upon consideration of ligand-receptor interactions and structure-activity data. Finally, the amino acid residues were indicated, mainly in TM helices 3-7, as potentially important in both AVP and DAVP docking. Among those Cys112, Val115-Lys116, Gln119, Met123 in helix 3; Glu174 in helix 4; Val206, Ala210, Val213-Phe214 in helix 5; Trp284, Phe287-Phe288, Gln291 in helix 6; and Phe307, Leu310, Ala314 and Asn317 in helix 7 appeared to be the most important ones. Many of these residues are invariant for either the GPCR superfamily or the neurophyseal (vasopressin V2R, V1aR and V1bR and oxytocin OR) subfamily of receptors. Moreover, some of the equivalent residues in V1aR have already been found critical for the ligand affinity.
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PMID:Molecular modeling of the human vasopressin V2 receptor/agonist complex. 974 70


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