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)

[3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies.
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PMID:Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones. 19 53

Antibovine neurophysin antibodies (anti-bNpI and/or anti-bNpII) are present in certain patients with familial central diabetes insipidus; these are exogenous origin, as they are not present in patients who have not received treatment with crude posterior pituitary extracts over the years preceding the analysis. Immunoreactive neurophysins were detectable in the blood of five patients with familial central diabetes insipidus, and in two of them, the levels increased after a short period of water restriction. There is marked polymorphism of these neurophysins from one serum to another: neurophysin I was consistently absent, while neurophysin II, accessory neurophysins, and other immunoreactive substances not present in normal sera were sometimes present in variable amounts. Immunoreactive AVP was undetectable in the urine of all patients, while immunoreactive OT was found in three of them; the latter substance could, however, be arginine vasotocin. Data are presented suggesting that the association between the biosynthesis of neurophysin I and AVP on the one hand, and neurophysin II and OT on the other hand is maintained in patients with isolated AVP deficiency on the basis of a congenital defect.
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PMID:Serum Neurophysins in familial central diabetes insipidus. 26 36

Using sensitive specific RIAs for vasopressin (AVP) and the two major human neurophysins, the relationship between AVP and the individual human neurophysins was investigated in man by measuring changes in plasma concentrations in physiological and pathological states known to be associated with changes in AVP secretion. Dehydration, water loading, and hemorrhage produced small but significant changes in plasma AVP concentrations without changes in the individual human neurophysins. In response to the stimulus of cigarette smoke inhalation, large parallel changes in plasma AVP and human neurophysin I (HNPI) levels were seen without change in plasma human neurophysin II (HNPII) levels. In the pathological states of diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion,the observations more strongly supported a specific association between AVP and NHPI. In eight patients with central diabetes insipidus, plasma AVP and HNPI levels were low or undetectable, while plasma HNPII levels were normal. There was a clear distinction of both plasma AVP and HNPI levels in patients with central diabetes insipidus and those in patients whti nephrogenic diabetes insipidus. In 14 patients with the syndrome of inappropriate antidiuretic hormone secretion due to causes other than ectopic AVP production from tumors, plasma AVP and HNPI levels were elevated or normal, while plasma HNPII levels were normal. There was a highly significant positive correlation (r = 0.99) between plasma AVP and HNPI levels in these patients, with a 1:1 molar ratio. These data suggest that the secretion of AVP and HNPI in man are functionally related, while the secretion of HNPII is independent of AVP secretion.
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PMID:Plasma vasopressin and human neurophysins in physiological and pathological states associated with changes in vasopressin secretion. 47 48

A radioimmunoassay for AVP capable of measuring human plasma AVP is described. Iodination was performed by the chloramine T method and purified by chromatography on Sephadex G-25. Specific activity of 125I-AVP was 1710 +/- 155 Ci/mmol. Antiserum of high affinity (Keq = 2.7 X 10(11) 1/mol) has been raised in rabbits, which shows slight cross-reactivity with LVP and negligible reactivity with oxytocin. The aqueous assay is capable of detecting 0.4 fmol of AVP/tube and it is highly reproducible. A F lorisil extraction technique is described in detail and gives recovery of 70% of synthetic AVP added to plasma over a wide physiological range. The lowest detectable concentration of plasma AVP is 0.3 pmol/l. The method has been validated by studying changes in plasma AVP concentration following overnight dehydration (plasma AVP =3.46 +/- 1.89 (SD) pmol/l), and water loading (plasma AVP = 1.54 +/- 0.59 pmol/l), P less than 0.005, in normal subjects. A highly significant positive correlation has been found between plasma AVP and plasma osmolality (r =+0.75). Plasma AVP concentration has also been determined in patients with DI and the syndrome of inappropriate ADH secretion. No effect was found on the level of plasma AVP in normally hydrated volunteers undergoing postural change but levels rose following strenuous exercise from basal concentrations of 1.57 +/- 0.59 pmol/l to 4.77 +/- 3.43 pmol/l, P less than 0.01.
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PMID:The development of a radioimmunoassay for the measurement of human plasma arginine vasopressin. 89 Oct 2

The effects of acute and chronic ketocyclazocine (KCZ, a kappa receptor agonist) and its interactions with oxytocin (OXY) or vasopressin (AVP) were investigated on food intake in free-fed rats. Acute treatment with KCZ (1 mg/kg) produced a generalized hyperphagia during the light phase (0-6 h) without influencing dark phase (6-24 h) food intake. On chronic administration, tolerance developed to hyperphagic effect during light phase, whereas an enhancement in the food intake was seen during dark phase. OXY or AVP (both at 10 micrograms/kg) per se, did not affect the food intake response during either the light or the dark phase, after acute as well as chronic treatment. In the interaction studies, acute AVP or OXY attenuated the hyperphagia of KCZ during the light phase. On chronic treatment, both AVP and OXY blocked (a) the tolerance, and (b) the "reverse tolerance" to the food intake response to KCZ during light and dark phases, respectively. These results are discussed in light of complex opioid-OXY/AVP interactions during food intake in rats.
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PMID:Effects of acute and chronic ketocyclazocine and its modulation by oxytocin or vasopressin on food intake in rats. 131 56

We characterized oxytocin (OT) receptors in purified plasma membranes from amnion, decidua, and myometrium of late pregnant rabbits using an iodinated OT antagonist (OTA). Saturation studies showed similar Kd values for specific binding sites in the 100- to 250-pM range in all three tissues. OT receptor concentrations in decidua and myometrium did not change until the day of labor (day 31), when they rose about 2.5- and 18-fold, respectively. Increases in amnion receptors were first apparent on day 28 and continued to maximal levels on day 31. There was an increase of about 230-fold from day 26 to labor, reaching 9.5 pmol/mg protein. Competition studies using analogs showed that ligand specificities of amnion and decidual membranes were indistinguishable. Those of myometrial membranes were somewhat different, possibly owing to the presence of both AVP receptors and OT receptors in the myometrium. Binding of OTA corresponded to the OT-induced release of prostaglandin E2 (PGE2) by amnion cells in culture. The effects of OT were dose dependent, agonist specific, and selectively inhibited by OTA. Amnion cells from days 22 and 28 did not respond significantly to either OT or phorbol 12-myristate 13-acetate (PMA), but cells from day 30 pregnant rabbits responded strongly to both. In contrast, calcium ionophore stimulated comparable amounts of PGE2 release from cells cultured on day 22, 28, or 30. These studies show that specific, high affinity OT receptors are associated with the release of PGE2 from rabbit amnion cells. Increases in amnion OT receptor and protein kinase-C activity precede by several days the increases in receptor concentrations in decidua and myometrium, suggesting important roles for the amnion and OT in the initiation of labor in rabbits.
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PMID:Characterization of oxytocin receptors in rabbit amnion involved in the production of prostaglandin E2. 131 89

The results are reported of a potentiometric and spectroscopic study of the H+ and Cu2+ complexes of Ala-Arg8-vasopressin (Ala-AVP) and oxytocin at 25 degrees C and an ionic strength of 0.10 mol dm-3 (KNO3). The coordination chemistry of oxytocin and Cu(II) has been shown to be virtually identical to that of Arg8-vasotocin, forming unusually stable complexes with four nitrogen coordination (4N complexes) below pH 7. Spectroscopic evidence suggests weak interaction between Cu(II) and the sulphur atom of the -Cys6- residue in the 2N species (pH congruent to 6) but this is absent in the 4N complex. Evidence is also presented for perturbation of electronic transitions within the aromatic ring of the Tyr residue by Cu(II). While the physiological potency of Ala-AVP is very high, its coordination chemistry differs significantly from that of Arg8-vasopressin. With Cu(II) it forms complexes of similar stability to those with tetraglycine, demonstrating that the addition of an alanyl residue to the amino-terminal of the peptide destroys the conformation which is particularly favorable for rapid 4N coordination.
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PMID:Potentiometric and spectroscopic studies of the Cu(II) complexes of Ala-Arg8-vasopressin and oxytocin: two vasopressin-like peptides. 132 87

A computerized telemetry system was used to monitor heart rate (HR), core temperature (CT), and gross locomotor activity in rats treated with saline or neuropeptides during a passive avoidance behavior task. Rats were exposed to a single mild footshock (0.15 mA, for 3 s). Retention tests were conducted at 24 and 48 h after the learning trial. One h prior to the 24-h retention test, each rat received one of the following treatments (SC): saline (SAL), desglycinamide [Arg8]-vasopressin (DG-AVP), ACTH4-10, or desglycinamide-oxytocin (DG-OXT), at a dose of 3 micrograms/rat for DG-AVP and DG-OXT, and 50 micrograms/rat for ACTH4-10. Rats treated with SAL showed a modest increase in avoidance latency accompanied by bradycardia at both retention tests. Rats receiving DG-AVP retained the highest avoidance latency among the experimental groups at both the 24- and 48-h retention test. These rats showed a decrease in HR of the same magnitude as the SAL-treated animals at both retention tests. Rats treated with ACTH4-10 showed an increase in avoidance latency during the 24-h but not during the 48-h retention test. In addition, following ACTH4-10 treatment, a tachycardiac response was found during the 24-h retention test. DG-OXT induced both behavioral and cardiac responses opposite to those found in rats given DG-AVP. CT gradually increased while the rats remained on the platform, irrespective of the treatment. Changes in HR and CT were not influenced by somatomotor activity, as no difference in gross locomotor activity was found among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of ACTH4-10, DG-AVP, and DG-OXT on heart rate and passive avoidance behavior in rats. 132 12

Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions.
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PMID:Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions. 142 42

The effects of postmortem delay on neuropeptide-containing perikarya was studied in the paraventricular nucleus (PVN) of the rat hypothalamus. Serial sections from brains kept in the skull after death for 6 h and immunocytochemically processed for oxytocin (OT), vasopressin (AVP) and corticotropin releasing factor (CRF) or hybridized in situ for CRF resulted in the well preserved phenotypic expression and stability of mRNA of the aforementioned neuropeptides. Furthermore in most cases, AVP and CRF expression was discernibly enhanced relative to prefixed immunopositive tissue. Results of this study suggest that postmortem variables do not significantly alter the neurochemical coding of magnocellular or parvocellular neurosecretory systems, and support the view that rat and human brain topography can be investigated from tissue left in situ after death for a relatively long period of time.
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PMID:Immunocytochemical and in situ hybridization detection of hypothalamic neuropeptides from postmortem unfixed rat brains. 147 56


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