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)

Adenylate cyclase and the [8-lysine]vasopressin receptor were solubilized from pig kidney medulla membranes using the nonionic detergent Triton X-100. Optimal conditions for solubilization were under continuous stirring in a medium containing 0.5% (/v) Triton X-100, 100 mM Tris-HCl, pH 8, and 10 mM MgCl2. Both adenylate cyclase activity and [3H][8-lysine]vasopressin binding activity were recovered in a -26,000 X g supernatant of detergent-treated membranes. The yield of solubilized adenylate cyclase was nearly 100%. The soluble enzyme was no longer sensitive to antidiuretic hormone but was slightly activated by sodium fluoride. The affinity of the soluble receptor for [8-lysine]vasopresin was les than that of the membrane-bound receptor (mean apparent Km values, respectively 10(-7) M and 2 X 10(-8) M), however binding cooperativity was preserved. Hill coefficients were 1.42 for the soluble receptor and 1.50 for the membrane receptor. The soluble receptor discriminated as efficiently as did the membrane receptor between [8-lysine-a1vasopressin and oxytocin. The yield of spolubilized receptor was only 30% despite the fact that all binding activity had disappeared from the residual pellet of detergent-treated membranes. When the membranous receptors were occupied before solubilization and the latter was performed under conditions in which dissociation of the hormone-receptor comples is slow, i.e. at low temperature, 65% to 100% of the hormone-receptor complex was recovered in the soluble fraction. The soluble hormone-receptor complex partially dissociated on rewarming whereas the free hormone concentration was kept unchanged in the medium. The residual binding capacity, which was 30% of the initial value, was identical with that determined when the receptor was solubilized in free form before incubation with labeled hormone. It was concluded that (a) solubilization of the receptor molecules was complete, (b) during solubilization two forms of the receptor appear, of which only one is accessible to the hormone, (c) occupancy of the receptor by the hormone prevented the formation of the nonaccessible form, and (d) some component or components of the soluble fraction might be responsible for the loss in apparent affinity.
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PMID:Solubilization of the [8-lysine]vasopressin receptor and adenylate cyclase from pig kidney plasma membranes. 17 Feb 74

Although the hypothesis that vasopressin and its associated neurophysin are synthesized together in one macromolecular common precursor was put forward more than a decade ago, direct conformation of this hypothesis has been lacking. A [35S]cysteine-labeled putative precursor for vasopressin-related neurophysin (Mr 20,000, pI 6.1) has been isolated from the supraoptic nuclei of rats. This precursor was subjected to limited proteolysis with trypsin which produced a Mr 10,000 protein and peptide products. The former was identified as neurophysin on the basis of its pH-dependent affinity for vasopressin and its behavior in isoelectric focusing systems (pI 4.6-4.8). The tryptic peptides proved to be vasopressin-like because they: (i) were rich in cysteine, (ii) comigrated with vasopressin on gel filtration columns in 6 M guanidine HCl, (iii) bound to a neurophysin-Sepharose affinity column at pH 5.7, and (iv) were recognized by antibodies against vasopressin. These data on the Mr 20,000, pI 6.1 protein represent direct experimental evidence for a candidate for the common precursor of vasopressin and neurophysin. We propose that this common precursor be called "propressophysin."
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PMID:Trypsin liberates an arginine vasopressin-like peptide and neurophysin from a Mr 20,000 putative common precursor. 29 5

Entirely beaded poly-N-acrylylpyrrolidine-co-bisacrylyl-1,2-diaminoethane-co-N-acrylyl-1,6-diaminohexane.HCl(PAP), a new resin on which to perform peptide chemistry, has been prepared by reverse phase suspension polymerization in quantitative yield. In addition to being a superior support to polystyrene, albeit readily adaptable to current techniques of peptide synthesis, its versatility has been furthur extended by the introduction and use of new peptide-to-polymer linking groups, which allow the use of the bidirectional approach to peptide chemistry. One such linkage, which connects the side chain of cysteine to PAP via an acid resistant S-carbamoyl bond, was used in a bidirectional synthesis of deamino-oxytocin. PAP solvates and swells in solvents with wide-ranging polarities, including aqueous media. Thus, peptide coupling reactions were performed in organic media of high and of low polarity as well as in aqueous solution.
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PMID:Poly-N-acrylylpyrrolidine. A new resin in peptide chemistry. 42 87

Chicken posterior pituitary tissue was partially fractionated by extraction with 0.1 M HCl followed by gel exclusion chromatography. Two fractions, B and C, bound oxytocin. Two components of fraction B and at least 1 component of fraction C had properties characteristic of mammalian neurophysins: they appeared to be synthesized in the hypothalamus, were depleted upon osmotic stress, were rich in residues of cysteine and the 2 components of B bound to [8-lysinel]-vasopressin coupled to Sepharose.
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PMID:Identification of neurophysin-like proteins in the posterior pituitary gland of the chicken (Gallus domesticus). 43 72

Endocrine responses to the serotonin (5-HT) 5-HT1C/5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were utilised to evaluate cocaine-induced alterations in postsynaptic 5-HT receptor function. Rats received cocaine HCl (0, 5 or 15 mg/kg i.p.) twice daily for 7 days. Effects of DOI (0, 0.5, 2 or 10 mg/kg i.p.) on plasma adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin and renin concentrations were assessed 42 h after the final cocaine injection. DOI dose dependently increased the plasma concentrations of each hormone. Cocaine potentiated the DOI-induced elevations of plasma ACTH, corticosterone and prolactin concentrations. In contrast, the oxytocin response was reduced, and the renin response was unaltered by cocaine exposure. The data suggest that 5-HT2 receptor-mediated responses for ACTH, corticosterone and prolactin secretion become supersensitive following repeated cocaine. In contrast, the 5-HT2 receptor-mediated response for oxytocin secretion is subsensitive. The cocaine-induced changes in postsynaptic 5-HT receptor function are likely a consequence of deficits in the function of 5-HT nerve terminals, that we have documented previously.
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PMID:Repeated cocaine modifies the neuroendocrine responses to the 5-HT1C/5-HT2 receptor agonist DOI. 133 68

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

We have analysed, with the aid of a novel radioiodinated oxytocin (OT)-receptor antagonist, the role of Mg2+ in uterine OT-receptor function. The antagonist-receptor interaction was characterized by high affinity, reversibility and stereospecificity in Tris/HCl buffer containing 3 mmol of Mg2+/litre as well as buffer free of Mg2+. By contrast, omission of Mg2+ decreased the affinity of the receptor for OT by about 1500-fold; moreover, the stereospecificity of agonist, but not antagonist, binding was lost. Since guanine nucleotides had relatively minor effects in this system (less than or equal to 2-fold decrease in OT affinity), we suggest that the agonist-binding site of OT receptors is directly modulated by Mg2+, unlike other receptors, where the effects of bivalent cations are exerted via guanine-nucleotide-binding (G-) proteins. Thus the ligand recognition mechanism of OT receptors may be novel in this respect.
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PMID:Essential role of magnesium in oxytocin-receptor affinity and ligand specificity. 253 90

The identity of the subtype of opioid receptor mediating morphine dependence in relation to oxytocin neurones was investigated. Virgin female rats were implanted with a subcutaneous osmotic minipump to infuse morphine continuously (up to 50 micrograms/h) into a lateral cerebral ventricle. After 5 days of morphine infusion, rats were anesthetized with urethane, and the electrical activity of electrophysiologically identified supraoptic neurones was recorded extracellularly while opioid antagonists were injected i.v. Putative oxytocin cells were excited following low doses of naloxone HCl: 4/7 cells were excited by 1 microgram/kg, 6/7 cells by 2.5 micrograms/kg, and 11/13 cells by doses of 5-50 micrograms/kg. MR2266 ((-)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan: an antagonist with much greater affinity for kappa-subtype opioid receptors than naloxone) excited oxytocin cells less potently: none of 9 cells was excited by 10 micrograms/kg MR2266, 2/4 cells were by 25-50 micrograms/kg, 3/9 cells by 100 micrograms/kg and only 4/8 by 200-500 micrograms/kg. At low concentrations naloxone is selective for mu-subtype opioid receptors, hence the morphine dependence of oxytocin neurones is probably via mu-receptors. Naloxone methylbromide (MRZ), a quaternary ammonium derivative of naloxone, excited oxytocin cells in morphine-treated rats, but was at least 10 times less potent than naloxone. Thus part of the morphine-withdrawal excitation of oxytocin neurones may be mediated by mu-receptors outside the blood-brain barrier.
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PMID:Sensitivity of magnocellular oxytocin neurones to opioid antagonists in rats treated chronically with intracerebroventricular (i.c.v.) morphine. 271 89

It was examined whether the digoxin-like immunoreactive substance (DLIS) extracted from cord blood has a natriuretic activity. The DLIS was prepared from cord blood of healthy fullterm infants by acetone-HCl extraction and a gel filtration column. A solution (solution A) containing 1.0 ng/ml of DLIS or another solution (solution B) consisting of solution A from which the DLIS had been completely absorbed by rat brain synaptosome, a crude digoxin receptor, were infused directly into the renal arteries of rats. Serum and urine were serially sampled. The excretion of sodium into the urine increased gradually after the initiation of infusion and reached a level two or three times higher than that before infusion (p less than 0.05). The infusion of a buffer solution or of the extract from which the DLIS had been absorbed by rat brain synaptosome did not significantly increase the urinary excretion of sodium. Statistical analysis showed a clear difference in the natriuretic activity between solutions A and B (p less than 0.01, p less than 0.05). Well-known natriuretic substances such as atrial natriuretic hormone, prostaglandin E2, F2 alpha, bradykinin and oxytocin dopamine were not detected enough to contribute to natriuresis in the extracts. From this data, we speculated that the DLIS in cord blood has a natriuretic activity and that it plays a role in water and sodium homeostasis in perinatal life.
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PMID:Natriuretic activity of digoxin-like immunoreactive substance extracted from cord blood. 282 60

In addition to its peripheral endocrine actions, arginine vasopressin (AVP) has been implicated in the central control of blood pressure. Intracerebroventricular (i.c.v.) injections (0.01-1.0 nmol) of AVP or arginine vasotocin (AVT), but not oxytocin (OXY), into unanesthetized rabbits caused a rapid, dose related rise in blood pressure as well as increases in heart rate. The lowest centrally administered dose of AVP and AVT (0.01 nmol) had no effect on blood pressure when given intravenously. In search of tissue locus for the pressor effect of AVP microinjection of AVP and OXY into the posterior hypothalamus and septum of conscious rabbits was without effect. However, microinjection (0.01-0.04 nmol) of AVP into the nucleus tractus solitarius of anesthetized rabbits caused a rise in blood pressure similar to the response seen after i.c.v. injection. Comparable volumes of the vehicle into the ventricle or the tissue sites had no effect on resting blood pressure. The pressor response after AVP given i.c.v. was significantly reduced up to 3 h after administration of the ganglionic blocker, chlorisondamine HCl. The central antagonist, d(CH2)5Tyr (Me) vasopressin, eliminated the usual increase in blood pressure after administration of AVP in half the animals tested. The results indicate that AVP acts centrally to mediate cardiovascular responses in unanesthetized as well as anesthetized rabbits.
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PMID:The action of centrally administered arginine vasopressin on blood pressure in the conscious rabbit. 293 25


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