UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of interleukin-1 (IL-1) induces increases in plasma ACTH and glucocorticoids. Numerous experiments have implicated the hypothalamic CRH neurosecretory system in these responses, but have failed to provide evidence for involvement of the ACTH secretagogue vasopressin (VP). The rat CRH neurosecretory system contains two types of cells: VP expressing and VP deficient. Hence, the above findings suggested that IL-1 may selectively activate the VP-deficient subtype of CRH neurosecretory cells. In this study we employed postembedding electron microscopic immunocytochemistry to directly assay IL-1-induced depletion of secretory vesicles from identified VP-expressing and VP-deficient CRH neurosecretory axons. IL-1-induced depletion of secretory vesicles from these axons was correlated with increases in plasma ACTH and decreases in plasma PRL. No dose of IL-1 was found that could selectively activate one subtype of CRH neurosecretory axons; at doses of 0.67 microgram/100 g and above for both IL-1 alpha and IL-1 beta, equal depletion of vesicles from the two subtypes was observed. Similar results were previously found after the injection of bacterial lipopolysaccharide, which induces the release of IL-1 from macrophages. The findings unequivocally establish for the first time that IL-1 activates hypothalamic CRH neurosecretory cells in the absence of surgical stress, anesthesia, disruption of the infundibular area, or administration of toxic drugs. In addition, these data clearly demonstrate that IL-1 induces the release of VP from neurosecretory axons in the portal capillary zone of the external zone of the median eminence. Previous studies have shown that the VP-deficient subtype of CRH neurosecretory axons is not strongly activated by several types of stress; therefore, activation of the system by inflammatory mediators involves mechanisms different from those mediating the stress response.
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PMID:Effects of interleukin-1 on the stress-responsive and -nonresponsive subtypes of corticotropin-releasing hormone neurosecretory axons. 131 22

It has been reported that cells of the immune system produce and release considerable amounts of pro-opiomelanocortin (POMC) -derived peptides in response to coculture with a variety of stimulatory agents. The present study investigated whether extracts of human peripheral blood mononuclear cells (PBMC) contain immunoreactivity for beta-endorphin (beta E) and related peptides. Using four endorphin RIA systems with different specificities, extracts of freshly isolated PBMC and PBMC cultured in the presence or absence of mitogens or of corticotropin releasing factor (CRF) and vasopressin (VP), were analyzed. With a radioimmunoassay (RIA) system directed to the midportion of beta E, immunoreactivity (MP beta E-IR) was readily detectable, although the concentration was extremely low (ca. 200 pg/10(7) cells). beta E immunoreactivity (beta E-IR) and alpha-endorphin immunoreactivity (alpha E-IR), as determined in C-terminally directed RIA systems, were present in even lower concentrations. gamma-Endorphin immunoreactivity (gamma E-IR) was hardly detectable. Of subsets enriched in T-cells, B-cells or monocytes, the highest concentration of MP beta E-IR was detected in extracts of monocytes. Coculture of PBMC with the mitogen Concanavalin A (Con A) or Phytohaemagglutinin (PHA) increased the amount of MP beta E-IR in extracts of the cells. No increase in alpha E-IR, however, was detected, whereas beta E-IR was only increased in extracts of cells cultured in the presence of Con A. No increase, in any of the immunoreactivities, was observed in extracts of PBMC cultured with bacterial lipopolysaccharide (LPS) or with the combination of CRF and VP, both stimuli that have been reported to induce POMC peptides in cultured PBMC. The present data show that human PBMC contain endorphin-like immunoreactivity, but in very small amounts. The extremely low concentrations and the ineffectiveness of LPS and the combination of CRF and VP to increase the endorphin-like immunoreactivity raise questions about the reported capacity of PBMC to synthesize POMC-derived peptides.
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PMID:Endorphin-like immunoreactivities in uncultured and cultured human peripheral blood mononuclear cells. 137 Nov 79

Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action. 164 Oct 72

1. The effects on blood pressure and on pressor responses to noradrenaline (NA), of NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), inhibitors of the L-arginine/nitric oxide pathway, were investigated in anaesthetized rats receiving an infusion of bacterial endotoxin (E. coli lipopolysaccharide, LPS). 2. Infusion of LPS (10 mg kg-1 h-1) for 50 min had no effect on mean arterial blood pressure (MABP) but induced a reduction in responsiveness to noradrenaline (100 ng-1 micrograms kg-1). L-NMMA (30 mg kg-1), but not D-NMMA, caused an increase in MABP of approximately 30 mmHg and restored responses to NA. This effect was reversed by L- but not D-arginine (100 mg kg-1). 3. In LPS-treated rats, blood pressure responses to NA were only marginally increased by the cyclooxygenase inhibitor, indomethacin (5 mg kg-1). L-NAME (1 mg kg-1) caused a similar increase in MABP and restored pressor responses to NA both in the presence and absence of indomethacin. 4. Co-infusion of vasopressin (100 ng kg-1, for 10 min) with LPS (10 mg kg-1 h-1) in order to reproduce the hypertensive effect of L-NMMA and L-NAME increased pressor responsiveness to 100 and 300 ng kg-1 NA but not to 1 microgram kg-1 NA. 5. Infusion of sodium nitroprusside (30 micrograms kg-1 min-1) decreased responsiveness to NA even when the hypotension was corrected by co-infusion of vasopressin (50 ng kg-1 min-1). 6. These results demonstrate that the restoration of vascular responsiveness to NA in LPS-treated anaesthetized rats by inhibitors of the L-arginine/nitric oxide pathway is stereospecific and reversible. Furthermore, the experiments involving indomethacin suggest that although cyclo-oxygenase products of arachidonic acid may contribute to the development of LPS-induced hyporeactivity, the effect of L-NAME is unlikely to involve inhibition of the cyclo-oxygenase pathway. Comparison of NA responsiveness during vasopressin and L-NMMA/L-NAME-induced hypertension shows that increasing the blood pressure may modify LPS-induced hyporeactivity, but cannot account for the complete restoration of responses to NA by L-NMMA and L-NAME. These observations suggest that activation of nitric oxide formation from L-arginine makes a direct contribution to the production of vascular hyporeactivity by LPS in vivo.
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PMID:The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. 190 34

The cyclic undecapeptide cyclosporine A (CsA) is a potent immunosuppressive agent that inhibits the initial activation of T lymphocytes. This agent appears to be most effective in blocking the action of mitogens such as concanavalin A and the calcium ionophore A23187, which cause an influx of Ca2+, but not those that may act by alternate mechanisms. These observations suggest that CsA may block a Ca2+-dependent step in T cell activation. We have shown that stimulation of the T3-T cell receptor complex-associated Ca2+ transporter activates the Na+/H+ antiport (Rosoff, P. M., and L. C. Cantley, 1985, J. Biol. Chem., 260: 14053-14059). The tumor-promoting phorbol esters, which are co-mitogenic for T cells, activate the exchanger by a separate pathway which is mediated by protein kinase C. Both the rise in intracellular Ca2+ and intracellular pH may be necessary for the successful triggering of cellular activation. In this report we show that CsA blocks the T3-T cell receptor-stimulated, Ca2+ influx-dependent activation of Na+/H+ exchange, but not the phorbol ester-mediated pathway in a transformed human T cell line. CsA inhibited mitogen-stimulation of interleukin-2 production in a separate cell line. CsA also inhibited vasopressin stimulation of the antiporter in normal rat kidney fibroblasts, but had no effect on serum or 12-O-tetradecanoyl phorbol 13-acetate stimulation. CsA did not affect serum or vasopressin or serum stimulation of normal rat kidney cell proliferation. CsA also had no effect on lipopolysaccharide or phorbol ester stimulation of Na+/H+ exchange activity or induction of differentiation in 70Z/3 pre-B lymphocytes in which these events are initiated by the protein kinase C pathway. These data suggest that mechanisms of activation of Na+/H+ exchange that involve an elevation in cytosolic Ca2+ are blocked by CsA but that C kinase-mediated regulation is unaffected. The importance of the Na+/H+ antiport in the regulation of growth and differentiation of T cells is discussed.
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PMID:Cyclosporine A inhibits Ca2+-dependent stimulation of the Na+/H+ antiport in human T cells. 301 82

Peritoneal cells from thioglycollate-stimulated mice were allowed to adhere to coverglasses for 2 h to give a dense monolayer of adherent cells greater than 95% of which were macrophages. After incubation with the tetra-acetoxymethyl ester of quin2, coverglasses were rinsed with Ca2+-free saline, oriented at a 45 degree angle in square cuvettes containing a magnetically driven stir bar, and analyzed for changes in quin2 fluorescence in a spectrofluorimeter. Such fluorescence, taken as an indication of intracellular calcium ion concentration ([Ca2+]i), increased as exogenous calcium ion concentration ([Ca2+]o) was raised to 1 mM. At [Ca2+]o approximately equal to 10 microM, [Ca2+]i = 72 +/- 14 nM (n = 26); at [Ca2+]o = 1 mM, [Ca2+]i = 140-220 nM, levels not increased by N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine, a membrane-permeant chelator of heavy metals than can quench quin2. Addition of mouse alpha + beta fibroblast interferon, lipopolysaccharide, thrombin, collagen, vasopressin, ADP, compound 48/80, or U46619 did not change [Ca2+]i. However, addition of platelet activating factor (PAF) (2-20 ng/ml) raised [Ca2+]i by 480 nM within 1 min if [Ca2+]o = 1 mM. In the presence of 5 mM EGTA, PAF raised [Ca2+]i by 25 nM. This suggests that PAF causes influx of exogenous Ca2+, as well as releasing some Ca2+ from intracellular stores. Consistent with these results, when PAF was added to 1 mM Ca2+ in the presence of 100 microM Cd2+ or Mn2+ to block Ca2+ influx, [Ca2+]i increased by only intermediate amounts; at the times of such dampened peak response, [Ca2+]i could be raised within 1 min to normal PAF-stimulated levels by chelation of the exogenous heavy metals with diethylenetriaminepentaacetic acid. Normal PAF responses were observed in the presence of indomethacin. The lowest dose of PAF observed to raise [Ca2+]i was 0.1 ng/ml. Response of [Ca2+]i to 2-20 ng/ml PAF was transient, and second applications had no effect. The PAF response also was seen in cell suspensions. These results suggest that an increase in [Ca2+]i may be an early event in PAF activation of macrophages.
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PMID:Platelet activating factor raises intracellular calcium ion concentration in macrophages. 373 74

The present study investigated the effect of the acute-phase response of a systemic immune activation on the transcription of various immediate early genes (IEGs) and neuropeptides in the brain of conscious rats. One, 3, 6, 9, and 12 h after a single intraperitoneal (i.p.) administration of either the immune activator lipopolysaccharide (LPS) or the vehicle solution, adult male rats were sacrificed and their brains cut in 30-microns coronal sections. mRNA encoding the IEGs c-fos and nerve growth factor inducible-B (NGFI-B), and neuropeptides corticotropin-releasing factor (CRF), oxytocin (OT), and vasopressin (AVP) were assayed by in situ hybridization histochemistry using a 35S-labeled riboprobes. The primary transcripts [heteronuclear (hn)RNA] for these neuropeptides were also detected using intronic probe technology, and colocalization of c-fos mRNA within CRF, AVP, and OT neurons was determined by means of a combination of immunocytochemistry and in situ hybridization techniques on same the brain sections. One h after LPS treatment, both c-fos and NGFI-B genes were expressed in the parvocellular division of the paraventricular nucleus (PVN) of the hypothalamus. The medial preoptic area/organum vasculosum of the lamina terminalis, the supraoptic nucleus (SON), the magnocellular division of the PVN, the arcurate nucleus/median eminence, the locus coeruleus, the nucleus of the solitary tract, and the area postrema also exhibited a strong signal for these two transcripts 3 h after endotoxin administration. A smaller but a significant c-fos expression was observed in various structures, including the dorsomedial hypothalamic area, the central nucleus of the amygdala, the ventral part of the tuberomammillary nucleus, the laterodorsal tegmental nucleus, the external lateral part of the parabrachial nucleus, the dorsal division of the ambiguus nucleus, and the lateral reticular nucleus of LPS-injected rats. The signal for c-fos and NGFI-B mRNA in most of these brain nuclei reached a maximum at 3 h postinjection, declined at 6 h, and vanished 9 to 12 h after LPS treatment. In the parvocellular nucleus of the PVN, c-fos was largely expressed in CRF-immunoreactive (ir) neurons, whereas in the magnocellular part of that nucleus and in the SON, this transcript was colocalized in numerous OT-ir and few AVP-ir neurons. Relative levels of CRF mRNA in the parvocellular PVN were also significantly increased 6 h following LPS, but endotoxin did not alter the genetic expression of this stress-related neuropeptide in other brain regions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuronal activity and neuropeptide gene transcription in the brains of immune-challenged rats. 749 92

Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but no change in adrenaline or noradrenaline levels was observed. All these effects were prevented or attenuated when the animals were pretreated intravenously with the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal expression of c-Fos were observed in hypothalamic regions concerned with thermoregulation, neurohypophysial secretion, and the control of pituitary-adrenocortical function. The stimulatory action of LPS in the median preoptic, supraoptic and paraventricular nuclei was prevented by IND, whereas IND given alone was without effect. These findings suggest that inducible cyclo-oxygenase pathways are responsible for the febrile and neuroendocrine effects of endotoxin in this species.
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PMID:Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig. 757 5

To identify brain neurons that participate in the acute phase response, rat brains were examined immunocytochemically for Fos protein following the intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS). Two to three hours after the injection of LPS, 150 micrograms/kg body weight, to adult male Long-Evans rats, a consistent anatomic pattern of Fos immunostained cell nuclei is seen. In the brain stem, prominant Fos immunostaining is induced in tyrosine hydroxylase immunoreactive neurons of the caudal ventral-lateral medulla (the A1 cell group), in both tyrosine hydroxylase positive and negative neurons of nu. tractus solitarius, in the parabrachial nu., and in a few neurons of the locus ceruleus. In the hypothalamus, endotoxin induces Fos expression in magnocellular neurons of the paraventricular and supraoptic nuclei and internuclear cell groups. A higher percentage of oxytocin-immunoreactive cells is double labeled for Fos nuclear immunostaining than vasopressin-immunoreactive cells. A minority of somatostatin immunoreactive periventricular hypothalamic neurons are Fos positive. Other hypothalamic nuclei that contain endotoxin-induced Fos nuclear immunostaining include the parvocellular neurons of the paraventricular nu., the dorsomedial and arcuate nuclei, the lateral hypothalamus, the dorsal hypothalamic area (zona incerta), and the median nucleus of the preoptic area. LPS induces numerous Fos-positive neurons in regions known to respond to a variety of stressful stimuli; these regions include the preoptic area, bed nucleus of the stria terminalis, lateral septum, and the central and medial nuclei of the amygdala. Moreover, Fos nuclear immunostaining is seen in neurons of circumventricular organs: the organum vasculosum of the lamina terminalis, the subfornical organ, and the area postrema. The maximum intensity of Fos nuclear immunostaining occurs 2-3 h after endotoxin administration and declines thereafter. It is attenuated by pretreatment with indomethacin, 25 mg/kg body weight Sc, or dexamethasone, 1 mg/kg IP. These observations are consistent with the participation of a variety of brain neuronal systems in the acute phase response and elucidate the functional neuroanatomy of that response at the cellular level.
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PMID:Anatomic patterns of Fos immunostaining in rat brain following systemic endotoxin administration. 771 98

We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL-1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered ACTH and corticosterone responses to interleukin-1 beta in male rats exposed to an alcohol diet: possible role of vasopressin and testosterone. 777 51

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