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)

Tetrodotoxin (TTX) was used to (1) distinguish between axonal and dendritic/somatic release of vasopressin (VP) and oxytocin (OT) within the supraoptic nucleus (SON) and (2) to determine whether neuronal inputs trigger intranuclear peptide release in the response to osmotic stimulation. Microdialysis was used to administer TTX (10(-6) M or 10(-4)M) bilaterally into the SON with simultaneous monitoring of central and peripheral peptide release and mean arterial pressure in urethane-anesthetized male rats. Osmotic stimuli were given via the microdialysis probe (1 M NaCl-artificial CSF) or injected intraperitoneally (3.5 M NaCl; 600 mu l/100 g b.w.) SON perfusion with TTX did not alter basal intranuclear VP or OT release or the intranuclear peptide response to direct NaCl stimulation of the SON. However, TTX treatment abolished the effect of peripheral osmotic stimulation on central peptide release. Basal plasma peptide levels were significantly reduced by TTX, e.g. decreases of 94.8 and 75.8% for VP and OT, respectively. TTX also blocked the peripheral endocrine and cardiovascular responses to both modes of osmotic stimulation. The TTX insensitivity of directly stimulated intranuclear release suggests nonsynaptic peptide release from dendrites and/or cell bodies. The ability of TTX to abolish the central peptide response to systemic osmotic stimulation demonstrates that intranuclear release is a part of a cascade produced by osmotic activation of multisynaptic pathways.
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PMID:Effects of tetrodotoxin on osmotically stimulated central and peripheral vasopressin and oxytocin release. 875 Dec 88

In mammals, the magnocellular neurons of the supraoptic nucleus (SON) have been classified into vasopressin- (VP) and oxytocin- (OT) producing subtypes. The degree to which these neurons have distinguishable characteristics is considered in the present review. Most of the cytoarchitectonic diversity observed in some Golgi studies has yet to be attributed to differences between OT and VP neurons. The predominant SON cell type is a large bipolar neuron with relatively short and simply branching dendrites. Based on intracellular filling, large multipolar neurons probably represent a small subset of neurosecretory cells. Parvicellular multipolar and bipolar neurons may represent interneurons or subsets of neurosecretory cells. Suggestive evidence that axonal origin and spine density may differ between OT and VP neurons remains to be confirmed in rat. Different fiber systems are thought to preferentially innervate VP or OT subgroups, but only rarely have inputs to OT and VP neurons been compared at the ultrastructural level. Potentially selective inputs to OT somata may derive from the raphe system and the nucleus of the solitary tract, whereas the apparent preferential innervation of VP neurons (e.g. from the A1 region of the ventrolateral medulla) is less certain because of the overlapping dendritic fields of OT and VP neurons. Electrophysiologically, OT and VP neurons are best distinguished in vivo by their reaction to gastric, cardiovascular and suckling stimuli. The firing patterns of activated OT and VP neurons often differ, but can transiently appear indistinguishable in vivo and especially in vitro. Classification in vitro without immunochemical labelling may be aided by the presence of phasic bursting (mostly in VP neurons) and by the differential response of these neurons to certain neurochemicals or to stimulation of certain inputs. The membrane properties of OT and VP neurons are generally similar in vitro, but the range of tests has not been extensive. The depolarizing afterpotential is more often exhibited by, but is not exclusive to, VP neurons.
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PMID:Morphological and electrophysiological classification of hypothalamic supraoptic neurons. 896 9

As secretogranin II is considered to be a marker for the regulated secretory pathway, its distribution in the hypothalamo-neurohypophyseal system of salt-loaded Wistar rats was studied in detail by immunocytochemistry. Although after an osmotic challenge both vasopressin and oxytocin neurons are stimulated, secretogranin II was exclusively expressed in a subpopulation of vasopressinergic magnocellular neurons in the supraoptic and paraventricular nucleus of Wistar rats. Secretogranin II was only surely visualized after a combination of osmotic challenge and blockade of axonal transport by colchicine treatment. When these pre-treatments were not performed, only punctate fibers situated around the magnocellular neurons within the paraventricular and supraoptic nucleus were observed. Oxytocinergic magnocellular neurons never displayed any secretogranin II immunoreactivity, not even during lactation and after colchicine treatment. These findings suggest that secretogranin II is of functional importance during enhanced secretory activity within vasopressinergic neurons.
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PMID:Specific expression of secretogranin II in magnocellular vasopressin neurons of the rat supraoptic and paraventricular nucleus in response to osmotic stimulation. 931 Mar 89

Electrophysiological and morphological characteristics of neurons in perinuclear zone of supraoptic nucleus. J. Neurophysiol. 78: 2427-2437, 1997. Neurons in the perinuclear zone (PZ) of the supraoptic nucleus (SON) are thought to serve as interneurons and may mediate changes in neurohypophysial hormone release in response to physiological changes in blood pressure. However, the morphology and electrophysiological characteristics of PZ neurons are unknown. In the present study, PZ neurons from male and female rats were recorded intracellularly to determine some membrane properties, then filled with biocytin or biotinamide for morphological analysis. In general, PZ neurons had faster spikes than magnocellular SON neurons, and the great majority were characterized by a subthreshold depolarizing hump when depolarized from a hyperpolarized (less than -80 mV) membrane potential. In most neurons, this hump was similar to low-threshold spikes described in other CNS regions. Near-threshold, fast action potentials were clustered near the onset of these depolarizations. Conspicuously absent in all PZ neurons was the strong transient and subthreshold outward rectification characteristic of vasopressin and oxytocin neurons of the SON. These results suggest that PZ neurons are electrophysiologically distinct from neurosecretory neurons of the SON. No differences were found between male and female rats in any of the basic properties examined, including input resistance, membrane time constant, spike height, spike width, spike threshold, and the size of the spike afterhyperpolarization. Morphologically, PZ neurons were diverse but were divided into spiny and aspiny groups. Three spiny neurons and one aspiny neuron contributed an axonal projection to the SON characterized by varicosities suggestive of terminals. In the case of the three spiny neurons, the SON projection was clearly a minor collateral projection. The axon arborized in the PZ, but one or more branches were cut at the edge of the explant, indicating a longer projection. In the remaining neurons, no axonal projection to the SON was detected and several had axons leaving the explant. Some portion of the dendritic tree penetrated the SON in several neurons. The morphology of PZ neurons was thus heterogeneous and suggests that, for some cells at least, the projection to the SON may be a minor collateral component of a much wider axonal projection.
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PMID:Electrophysiological and morphological characteristics of neurons in perinuclear zone of supraoptic nucleus. 935 94

The subcellular compartmentalization and axonal transport of oxytocin and vasopressin messenger RNAs have recently been reported in the rat hypothalamo-posthypophyseal system using in situ hybridization. So far, no data are available concerning the intracellular distribution of co-localized peptide transcripts, for example of galanin, which is synthesized in the vasopressinergic magnocellular neurons of the rat and which is up-regulated in these neurons under different conditions, including salt loading and colchicine injection. In the present study, using non-radioactive in situ hybridization and immunohistochemistry at the light and electron microscope levels, preprogalanin messenger RNA and galanin-like immunoreactivity were localized in the hypothalamo-posthypophyseal system. After salt loading, preprogalanin transcripts were found throughout the perikaryal cytoplasm, especially in the peripheral cytoplasm and in the perinuclear area. Since immunohistochemistry also showed galanin-like immunoreactivity preferentially in the perinuclear area of control rats, galanin synthesis may occur mainly in this cytoplasmic domain. Preprogalanin messenger RNA was also clustered in dendrites containing rough endoplasmic reticulum. The use of a new in situ hybridization method involving tyramide signal amplification, based on catalysed reporter deposition, allowed visualization of preprogalanin messenger RNA in axonal projections running through the internal layer of the median eminence after salt loading, but not in control or in colchicine-injected animals. The negative results obtained after colchicine injection indicate that the mechanism of messenger RNA transport may require an intact cytoskeleton. The labelling was found in non-dilated axon segments as well as in a subset of axonal swellings in the rostral aspect of the median eminence, but was restricted to a few swellings in its caudal part, with no labelling in the posterior pituitary. Thus, preprogalanin messenger RNA was segregated in the axons. The functional significance of messenger RNAs' exportation into axons is not known, but our results suggest that this phenomenon may not be limited to the two principal magnocellular hormone messenger RNAs, but may also involve co-existing peptide messenger RNAs.
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PMID:Subcellular localization of preprogalanin messenger RNA in perikarya and axons of hypothalamo-posthypophyseal magnocellular neurons: an in situ hybridization study. 957 92

F3, a glycoprotein of the immunoglobulin superfamily implicated in axonal growth, occurs in oxytocin (OT)-secreting and vasopressin (AVP)-secreting neurons of the adult hypothalamo-neurohypophysial system (HNS) whose axons undergo morphological changes in response to stimulation. Immunocytochemistry and immunoblot analysis showed that during basal conditions of HNS secretion, there are higher levels of this glycosylphosphatidyl inositol-anchored protein in the neurohypophysis, where their axons terminate, than in the hypothalamic nuclei containing their somata. Physiological stimulation (lactation, osmotic challenge) reversed this pattern and resulted in upregulation of F3 expression, paralleling that of OT and AVP under these conditions. In situ hybridization revealed that F3 expression in the hypothalamus is restricted to its magnocellular neurons and demonstrated a more than threefold increase in F3 mRNA levels in response to stimulation. Confocal and electron microscopy localized F3 in secretory granules in all neuronal compartments, a localization confirmed by detection of F3 immunoreactivity in granule-enriched fractions obtained by sucrose density gradient fractionation of rat neurohypophyses. F3 was not visible on any cell surface in the magnocellular nuclei. In contrast, in the neurohypophysis, it was present not only in secretory granules but also on the surface of axon terminals and glia and in extracellular spaces. Taken together, our observations reveal that the cell adhesion glycoprotein F3 is colocalized with neurohypophysial peptides in secretory granules. It follows, therefore, the regulated pathway of secretion in HNS neurons to be released by exocytosis at their axon terminals in the neurohypophysis, where it may intervene in activity-dependent structural axonal plasticity.
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PMID:Regulated expression of the cell adhesion glycoprotein F3 in adult hypothalamic magnocellular neurons. 965 Dec 16

Congenital panhypopituitarism is a rare disease. It may be a complication of tumors, craniocerebral trauma, infection, granulomatous diseases, vascular pathologies, etc. In many cases no primary disease causing panhypopituitarism is found (idiopathic form). A potential reason is interruption of the pituitary stalk due to ischemic etiology in patients with cord encirclement and/or other birth injuries leading to interruption of the axonal transport of ADH and oxytocin as well as hypothalamic releasing hormones. This explains the ectopy of the neurohypophysis without diabetes insipidus and the hypoplasia of the adenohypophysis. GH-deficiency causes short stature and metabolic disturbances, LH-FSH-deficiency amenorrhoea/oligomenorrhoea, loss of libido and secondary sexual characteristics, TRH-deficiency hypothyroidism and ACTH-deficiency hypotonia, weakness, loss of pigmentation. We report a case of congenital panhypopituitarism. MR imaging of the brain revealed a hypoplastic adenohypophysis and a hypoplastic pituitary stalk which was interrupted in its superior segment. An ectopic neurohypophysis was found located in the area of the hypothalamus ("hypothalamic hot spot"). The ectopic neurohypophysis showed strong enhancement after intravenous application of Gd-DTPA. MR imaging of the hypothalamic-hypophyseal axis is well suited for the differentiation between congenital and acquired forms of panhypopituitarism in clinically uncertain cases.
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PMID:[Neuro-MR-findings in primary panhypopituitarism]. 979 7

Dystrophin, utrophin and dystroglycan are present not only in muscle but also in brain. In muscle, they link the extracellular matrix to the cytoskeleton. Their function in brain is not understood. Here we show their presence in the hypothalamo-neurohypophysial system which secretes the neurohormones oxytocin and vasopressin. Using immunocytochemistry, we showed that dystrophins are present in the neurohypophysis of control rats. After water deprivation, immunoreactivity dramatically decreased and appeared in axonal swellings in the hypothalamic tract. Dystrophin immunostaining can be ascribed to dystrophin and/or utrophin as well as the DMD (Duchenne Muscular Dystrophy) gene short products Dp140 and Dp71 as revealed by Western immunoblots of synaptosomes isolated from neurohypophyses of control rats. In synaptosomes isolated from rats under water deprivation, the immunoreactivity entirely disappeared. Further biochemichal characterization of isolated neurosecretory granules (NSG) showed that Dp140 and Dp71 are enriched in the NSG stored in the swellings of the neurohypophysis whereas the NSG of the nerve endings are devoid of these proteins. In addition we observed that the presence of beta-dystroglycan and actin correlates with the presence of dystrophins. Our data favor a direct implication of the dystrophins and/or utrophin, dystroglycan and actin in the neurosecretory processes of the hypothalamo-neurohypophysial system.
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PMID:Dystrophins in neurohypophysial lobe of normal and dehydrated rats: immunolocalization and biochemical characterization. 985 64

In addition to the release of neurotransmitters from their axon terminals, several neuronal populations are able to release their products from their dendrites. The cell bodies and dendrites of vasopressin- and oxytocin-producing neurones are mainly located within the hypothalamic supraoptic and paraventricular nuclei and neuropeptide release within the magnocellular nuclei has been shown in vitro and in vivo. Local release is induced by a range of physiological and pharmacological stimuli, and is regulated by a number of brain areas; locally released peptides are mainly involved in pre- and postsynaptic modulation of the electrical activity of magnocellular neurones. Spatial and temporal differences between peptide release within the nuclei and that from the distant axonal varicosities indicate that the release mechanisms are at least partially independent, supporting the hypothesis of locally regulated dendritic release of vasopressin and oxytocin. In this respect, magnocellular neurones show similarities to other neuronal populations and thus autoregulation of neuronal activity by dendritic neuromodulator release may be a general phenomenon within the brain.
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PMID:Dendritic release of vasopressin and oxytocin. 987 Jul 45

Little is known regarding the effect of chronic changes in neuronal activity on the extent of collateral sprouting by identified CNS neurons. We have investigated the relationship between activity and sprouting in oxytocin (OT) and vasopressin (VP) neurons of the hypothalamic magnocellular neurosecretory system (MNS). Uninjured MNS neurons undergo a robust collateral-sprouting response that restores the axon population of the neural lobe (NL) after a lesion of the contralateral MNS (). Simultaneously, lesioned rats develop chronic urinary hyperosmolality indicative of heightened neurosecretory activity. We therefore tested the hypothesis that sprouting MNS neurons are hyperactive by measuring changes in cell and nuclear diameters, OT and VP mRNA pools, and axonal cytochrome oxidase activity (COX). Each of these measures was significantly elevated during the period of most rapid axonal growth between 1 and 4 weeks after the lesion, confirming that both OT and VP neurons are hyperactive while undergoing collateral sprouting. In a second study the hypothesis that chronic inhibition of neuronal activity would interfere with the sprouting response was tested. Chronic hyponatremia (CH) was induced 3 d before the hypothalamic lesion and sustained for 4 weeks to suppress neurosecretory activity. CH abolished the lesion-induced increases in OT and VP mRNA pools and virtually eliminated measurable COX activity in MNS terminals. Counts of the total number of axon profiles in the NL revealed that CH also prevented axonal sprouting from occurring. These results are consistent with the hypothesis that increased neuronal activity is required for denervation-induced collateral sprouting to occur in the MNS.
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PMID:Central peptidergic neurons are hyperactive during collateral sprouting and inhibition of activity suppresses sprouting. 1002 46


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