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 continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones.
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PMID:Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines. 18 90

Localization studies of the hypothalamohypophysial and tuberoinfundibular neurosecretory systems were performed in the adult male mallard duck with an immunoperoxidase techinque for the demonstration of neurophysin (NP) and gonado-tropin-releasing hormone (Gn-RH) and with aldehyde fuchsin for the staining of neuosecretory material (NSM). A comparison was made between the distribution of NSM stained with aldehyde fuchsin and NP seen by immunocytochemistry. The magnocellular perikarya of the supraoptic (SON) and paraventricular (PVN) nuclei, the zona externa of the anterior median eminence (ME), the fiber layer of both the anterior and posterior ME, and small neurons in the tractus quintofrontalis were stained by both the immunoperoxidase method for NP and by the aldehyde fuchsin stain. In contrast, the parvocellular neurons of the PVN, extra-hypothalamic neurosecretory fibers dorsal to the anterior commissure in the septal region and tanycytes lining the ventral 1/3 of the third ventricle at the level of the anterior ME, were stained only by the immunocytochemical procedure for NP. These observations indicate that immunocytochemistry is more sensitive than aldehyde fuchsin staining for detecting low concentrations of NP in cells and tissues, but the two techniques produce comparable results where the concentration of the NP is relatively high. Two populations of beaded axons containing Gn-RH were distributed throughout the zone externa of both the anterior and posterior ME. One group of fibers paralleled the hypothalamo-hypophysial neurosecretory tract whereas the other was distributed in the contact zone of the ME. Immunoreactive Gn-RH was found in the cytoplasm of a sparse population of cell bodies in the dorsolateral portion of the arcuate nucleus as well as in the axons that project from this nucleus ventrally towards the ME.
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PMID:Neurosecretory pathways in the mallard duck (Anas platyrhynchos) brain: localization by aldehyde fuchsin and immunoperoxidase techniques for neurophysin (NP) and gonadotrophin releasing hormone (Gn-RH). 79 39

Ten micrograms of PG F2 alpha in distilled water were injected intraperitoneally into thirty non-pregnant female rats and their hypophysis was studied after aldehyde-fuchsin and performic acid-alcian blue staining. A definite depletion of posterior pituitary principle was observed in the hypophysis. The role of oxytocin in relation to the oxytocic effect of prostaglandin F2 alpha is discussed.
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PMID:Effect of prostaglandin F2 alpha on the neurohypophysis. A histochemical study. 121 Dec 59

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

Light microscopic observations using Nomarski interference contrast optics or darkfield optics on unstained aldehyde-fixed vibratome sections of hypothalami from normal young adult male and female Long Evans rats and from vasopressin-deficient Brattleboro rats, revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions of globular or filamentous appearance in their somata. These inclusions were morphologically distinct from the large lipid droplets present in vasopressinergic magnocellular neurons of diabetes insipidus mice. Small portions of the vibratome sections containing the birefringent cells were excised and prepared for correlative electron microscopy. This revealed that the birefringent inclusions represented electron-dense material within cisterns of endoplasmic reticulum in magnocellular neurons. Antibodies to oxytocin or oxytocin-associated neurophysin immunolabelled the intracisternal electron-dense material and neurosecretory granules in resin-embedded ultrathin sections. Antibodies to vasopressin or vasopressin-associated neurophysin, and a panel of lectins did not label the intracisternal material. Quantitation revealed a small increase in the numbers of birefringent cells in aged rats and in rats drinking saline for 3 days. Subcutaneous injection of oestradiol benzoate for 7 days prior to fixation caused a large increase. After cessation of oestradiol administration the numbers of birefringent cells decreased; observations on the remaining cells showed that the endoplasmic reticulum cisterns were frequently fused with the plasmalemma, resulting in direct release of neurosecretory material into the extracellular spaces.
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PMID:Peptide accretions in the endoplasmic reticulum of magnocellular neurosecretory neurons in normal and experimentally manipulated rats. 181 Sep 24

Intraovarian pressure (IOP) of 5, 15, and 25 mm Hg was administered in the frog, Rana tigrina, and the response of the nucleus preopticus (NPO) pars magnocellularis was investigated with aldehyde fuchsin (AF) stain and immunocytochemical method using neurophysin (NP) antisera. The 5 mm Hg IOP treatment resulted in cell and cell nuclear hypertrophy (P less than 0.001); discrete signs of de novo synthesis of AF-positive and NP-immunoreactive material in the perikarya and remarkable increases in the number and size of "Herring bodies" in the processes were observed. Stimulatory response after 15 mm Hg IOP treatment was characterized by dramatic augmentation of the AF-positive and NP-immunoreactive material in the processes; the engorged and coalescing Herring bodies totally predominated the lateral preoptic area. IOP of 25 mm Hg resulted in extensive loss of secretory material; the processes revealed the presence of vacuoles indicative of the rapid anterograde transport of the neurosecretory material. Furthermore, the application of IOP seemed to promote the transport of NP-immunoreactive material toward the anterior preoptic area and amygdala pars medialis and the release of secretory material into the cerebrospinal fluid. No changes were observed in the NPO when treatment was preceded by the transection of ipsilateral dorsal spinal nerve roots or the spinal cord. The results suggest the existence of an afferent neural pathway from the ovary capable of conducting the stretch signals to the NPO and triggering the synthesis and release of neurohypophysial hormones.
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PMID:The response of nucleus preopticus neurosecretory cells to ovarian pressure in the frog, Rana tigrina. 228 85

In adrenalectomized rats the influence of salt loading or salt deprivation on the vasopressin and oxytocin content of the median eminence (ME) and the neural lobe (NL) was studied by means of various methods: morphometric and microphotometric analysis of aldehyde fuchsin-stained sections of ME and NL; immunohistochemical demonstration of neurophysin, oxytocin, and vasopressin in the ME and in the NL; radioimmunological measurement of oxytocin and vasopressin in the ME and in the NL. Adrenalectomy in salt-substituted rats raised the vasopressin content of the outer layer of the ME (OLME) but had no influence on the amount of vasopressin in the inner layer of the ME and in the NL. Osmotic stimulation of adrenalectomized rats by hypertonic saline markedly diminished vasopressin and oxytocin in the inner layer of the ME and in the NL but did not, or only slightly reduced vasopressin in the OLME. Withdrawal of salt supplementation in adrenalectomized rats resulted in a decrease of plasma sodium and plasma volume. It did not change the vasopressin or oxytocin content of the inner layer of the ME and of the NL, but it was correlated with a decrease of vasopressin in the OLME. The present findings may suggest that vasopressin in the OLME is involved in salt and/or volume regulation by influencing the hypophysial-adrenal axis.
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PMID:Effect of salt loading and salt deprivation on the vasopressin and oxytocin content of the median eminence and the neural lobe in adrenalectomized rats. 353 20

The distribution of dopamine (DA)-containing fibers in the virtual absence of noradrenaline (NA)-containing ones has been mapped by aldehyde fluorescence histochemistry in rats subjected to a combined neurotoxin treatment (intracerebral 6-hydroxydopamine injections plus systemic injections of the selective NA neurotoxin DSP-4). This pretreatment left di- and telencephalic DA levels largely unaffected, but reduced the NA levels by at least 86-96%. The resulting DA:NA ratios suggested that the catecholamine-containing structures, demonstrable by fluorescence histochemistry in the di- and telencephalic regions, were predominantly the DA-containing ones. While the distribution of DA terminal systems in the neo- and allocortical regions conformed well to previous results, the combined neurotoxin treatment revealed new features of the distribution of DA fibers in the diencephalon. In addition to the previously described innervations of the tubero-hypophyseal system, the incerto-hypothalamic system, and the mesohabenular pathway, previously unknown innervations were revealed in the supraoptic, paraventricular and dorsomedial nuclei of the hypothalamus, and in the paraventricular nucleus of the thalamus. Apart from some scattered fibers in the periventricular and lateral hypothalamic areas and medical zona incerta, other diencephalic nuclei seemed to be devoid of any significant DA terminal networks. The dopaminergic nature of these innervations is supported by DA uptake experiments (evaluated by fluorescence histochemistry) as well as by independent biochemical and immunohistochemical evidence. It is suggested that the DA innervations of the hypothalamic neurosecretory nuclei originate in cell bodies of the diencephalic A11-A14 cell groups and that such intradiencephalic DA projections participate in the regulation of oxytocin and vasopressin release from the pituitary.
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PMID:Selective histochemical demonstration of dopamine terminal systems in rat di- and telencephalon: new evidence for dopaminergic innervation of hypothalamic neurosecretory nuclei. 646 73

The influence of adrenalectomy and administration of hypertonic saline on the amount of vasopressin, oxytocin, and neurophysin contained in the median eminence and the neural lobe of rats was studied by means of the following methods: (i) morphometric and microphotometric analyses of aldehyde fuchsin-stained histological sections of the neurohypophysis; (ii) immunohistochemical demonstration of vasopressin, oxytocin, and neurophysin in the neurohypophysis, and (iii) radioimmunological measurement of vasopressin and oxytocin in extracts of the median eminence and the neural lobe. Adrenalectomy increases the amount of vasopressin and neurophysin in the external layer of the median eminence but does not change the content of oxytocin. It has no influence on the amount of vasopressin, oxytocin, and neurophysin demonstrable in the inner layer of the median eminence and in the neural lobe two weeks after the operation. Hypertonic saline markedly diminishes the vasopressin, oxytocin, and neurophysin content of the inner layer of the median eminence and the neural lobe but reduces only slightly, if at all, the amount of vasopressin and neurophysin in the outer layer of the median eminence. The findings support the concept that osmotic stress reduces only the vasopressin and oxytocin content of the hypothalamus-neural lobe system and has no or only little influence on the vasopressin content of the outer layer of the median eminence.
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PMID:Effect of adrenalectomy and administration of hypertonic saline on the content of aldehyde fuchsin-positive neurosecretory material and posterior lobe hormones in the median eminence and the neural lobe of rats. 683 20

Research on synthetic peptides at the Institute for Drug Research (IDR) is exemplified by an overview of the projects that resulted in significant results. The first synthesis of oxytocin, a pituitary hormone, in 1953 launched the research on synthetic peptides all over the world. This synthesis was reproduced by Bodanszky at the IDR in 1954, then, after some improvements, the process was presented to Richter to produce synthetic oxytocin for therapeutic purposes. Significant result was the first synthesis of the 39-member whole molecule of human ACTH, another pituitary hormone. A short SAR study on luteinizing hormone-releasing hormone (LHRH) led to an interesting analog, Cit-8-LHRH, and somewhat later, to the D-Cit-6-LHRH analogues, of which SB-75 become marketed under the name Cetrorelix. Studies on the brain peptides, enkephalins, resulted in GYKI-14,238, the first analog that showed analgesic activity upon systemic administration and whose human efficacy could also be proven during clinical examination. Significant results were also achieved in the research on anticoagulant peptides. The first highly potent peptide aldehyde inhibitor of thrombin, GYKI-14,166, was identified at the IDR as well as its stable analog, GYKI-14,766. This compound was selected for detailed preclinical study, licensed to Eli Lilly Company, got the generic name efegatran, and entered clinical trials. The first non-covalent peptide inhibitor of thrombin, GYKI-14,525, was also identified at the IDR. Thus IDR really provided the prototype of original thrombin inhibitors in the mid 70's, and analogues were prepared in many laboratories through two decades. IDR's current research program's objective includes a quest for peptide originals that can inhibit both thrombin and factor Xa in solution and also within plasma clots in which these enzymes are entrapped. Structures with such inhibitory profile were identified among the efegatran-related alpha-hydroxy acid and ethoxycarbonyl-amino acid derivatives. The follow-up molecules are even more promising as antithrombotics, and may also be useful for treatment of disseminated intravascular coagulation, an often fatal syndrome, so we continue working on this project.
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PMID:[Research on synthetic peptides of biological interest]. 1176 93


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