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)

A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones.
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PMID:Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract. 20 Mar 7

In adrenalectomized rats, histochemical and immunohistochemical properties of the following secretion products have been investigated: 1. CRF-granules in the outer layer of the median eminence; 2. neurosecretory material (NSM) in the supraoptico-hypophysial system of the hypothalamus; 3. secretory granules in the TSH-cells of the anterior lobe of the hypophysis; 4. secretory granules in the ependymal cells of the subcommissural organ (SCO); 5. beta-cell-granules in the islets of Langerhans in the pancreas. All these substances are characterized by their stainability with the so-called "Gomori method". The experiments have included studies into: a) the extractability of the substances by various solvents; b) the digestability of the substances by pepsin or trypsin; c) their histochemically detectable content of disulfide groups, arginine and periodic acid-Schiff (PAS) reactive carbohydrates; d) their reaction with porcine-neurophysin-II-antibodies. All substances exhibited a positive reaction for disulfide groups. Based on their solubility properties, their resistance to pepsin or trypsin, their respective content of PAS-reactive carbohydrates and their failure to react with anti-neurophysin serum the "Gomori-positive" granules in TSH-, SCO- and pancreatic beta-cells can be distinguished from one another and from CRF- and neurosecretory granules. In contrast, CRF-granules and NSM showed identical properties. Taking into consideration data from the biochemical and histochemical literature, the present findings suggest that CRF-granules and NSM consist of closely related biochemical substances.
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PMID:Histochemical and immunohistochemical properties of the CRF-granules and other "Gomori-positive" substances of the rat. 76 9

Light microscopic observations using Nomarski optics on the aldehyde-fixed hypothalamus of normal adult cats, monkeys and rabbits revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions. Immunogold labelling showed that in each species the cells displayed oxytocin-like immunoreactivity, both in electron-dense inclusions within some (but not all) cisterns of rough endoplasmic reticulum and in secretory granules. The cells in cats and rabbits were in all respects indistinguishable from the homologous 'birefringent' cells previously described in rats, but in monkeys, cells frequently contained additional inclusions in cisterns of rough endoplasmic reticulum which did not display oxytocin or vasopressin-like immunoreactivity, even after trypsin, pepsin or chymotrypsin treatment of sections. Observations on cats and rabbits using fluorescence microscopy revealed that the birefringent cells possessed bright autofluorescence which facilitated the identification of more cells than were seen using Nomarski optics alone. Autofluorescence was abolished when sections were mounted in glycerol, or when exposed to light for protracted periods of time. Attempts to label for monoamines in these cells were not successful, suggesting that the fluorescence is not due to aldehyde-induced amine fluorescence. It is not clear why neuropeptides are retained in some rough endoplasmic reticulum cisterns. It is possible that these birefringent cells contain a peptide, or peptides, which are abnormal in some manner, or which may be other members of the oxytocin gene family. Alternatively, the processing of neuropeptides to permit their export to the Golgi apparatus may be deficient. Acetylcholinesterase (AChE) histochemistry revealed that, unlike other oxytocin neurons, cells with intracellular accretions lacked detectable acetyl cholinesterase. As AChE is a known peptidase, it may be involved in regulating peptide export from the rough endoplasmic reticulum.
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PMID:Neuropeptide accretions in the endoplasmic reticulum of oxytocinergic neurons in cats, monkeys and rabbits: a widespread phenomenon. 129 66

A 32 year old I P II G with preexisting diabetes insipidus was treated with 1-(3-mercaptopropionic acid)-8-d-arginine vasopressin (DDAVP) during pregnancy. An otherwise normal pregnancy was marked only with an excessive weight increase. A healthy girl was delivered by secondary cesarean section at term. Postoperative the mother developed a water intoxication accompanying oxytocin-infusion. During nursing the diabetes insipidus improved significantly whereby DDAVP doses could be reduced to 20-10 percent. We suppose an overreaction to endogene oxytocin with an antidiuretic effect.
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PMID:[Pregnancy in diabetes insipidus--a case report with review of the literature]. 222 Jan 71

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

The completed amino-acid sequence of bovine neurophysin-II, a major neurohypophyseal hormone-binding protein in the hypothalamo-neurohypophyseal complex of cows, set the stage for the localization of the disulfide bonds of this sulfur-rich molecule. Neurophysin-II was digested with subtilisin or a pepsin-trypsin mixture. The resulting peptides were subjected to first-dimensional electrophoresis at pH 6.5, oxidized with performic acid, and subjected to second-dimensional electrophoresis under identical conditions as the first-dimensional separation, but in a perpendicular direction. Cysteic acid peptides were eluted (several after additional electrophoretic purification at pH 3.5) for amino-acid composition and NH(2)- and COOH-terminal analyses. Our assignment of the seven disulfide bridges present in neurophysin-II is as follows: Cys(10)-Cys(93); Cys(13)-Cys(95); Cys(21)-Cys(27); Cys(28)-Cys(44); Cys(54)-Cys(61); Cys(67)-Cys(73); Cys(74)-Cys(79). The assignment of disulfide bridges associated with Cys(27) and Cys(28) is tentative as it is derived from evolutionary consideration. The high disulfide content reduces drastically the allowed number of biofunctional conformers of neurophysin-II. It is suggested that neurophysin-II possesses a globular topography with minimal alpha-helix structure.
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PMID:Covalent structure of bovine neurophysin-II: localization of the disulfide bonds. 456 11

Peptide therapeutics have traditionally faced many challenges including low bioavailability, poor proteolytic stability and difficult cellular uptake. Conformationally constraining the backbone of a peptide into a macrocyclic ring often ameliorates these problems and allows for the development of a variety of new drugs. Such peptide-based pharmaceuticals can enhance the multi-faceted functionality of peptide side chains, permitting the peptides to bind cellular targets and receptors necessary to impart their role, while protecting them from degrading cellular influences. In the work described here, we developed three cyclic peptides, VP mimic1, VP mimic2 and OT mimic1, which mimic endocrine hormones vasopressin and oxytocin. Making notable changes to the overall structure and composition of the parent hormones, we synthesized the mimics and tested their durability against treatment with three proteases chosen for their specificity: pepsin, alpha-chymotrypsin, and pronase. Vasopressin and oxytocin contain a disulfide linkage leaving them particularly vulnerable to deactivation from the reducing environment inside the cell. Thus, we increased the complexity of our assays by adding reducing agent glutathione to each mixture. Subsequently, we discovered each of our mimics withstood protease treatment with less degradation and/or a slower rate of degradation as compared to both parent hormones and a linear control peptide.
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PMID:A comparative protease stability study of synthetic macrocyclic peptides that mimic two endocrine hormones. 2331 70

Oxytocin (Oxt) is considered as a potential agent to treat multiple neuropsychiatric disorders, obesity and metabolic syndrome. Although the mechanisms underlying these effects remain unclear, nasal administration is considered to be a potential way to deliver Oxt into blood vessels. The development of an easier, more stable and efficient way is expected. A recent study demonstrated that orally administered Oxt can be transmitted into blood if it is prevented from degradation in stomach and reaches the intestinal tract. In this study, we pretreated mice with a proton pump inhibitor (PPI), omeprazole (20 mg/kg), and administered capsulized Oxt (0.25 mg), so that the Oxt can be prevented from degradation by pepsin due to the low pH in stomach and reach the intestinal tract. Functionally, these mice showed a similar decrease in food intake to those who underwent intraperitoneal administration. We also confirmed that this method dramatically increased plasma Oxt levels and the expression of neural activation marker c-Fos protein in the paraventricular and suprachiasmatic nucleus. Our study showed that by pretreating mice with PPI, Oxt in a gelatin-coated capsule can prevent Oxt from degradation by pepsin in stomach, and reach the bloodstream in an effective concentration. These results indicate that our method is a promising oral delivery of Oxt and should be investigated further for other peptide agents based on peripheral injection or nasal administration.
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PMID:Oral oxytocin delivery with proton pump inhibitor pretreatment decreases food intake. 3229 73