Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Inflammatory mediators include endotoxin (ETX), cytokines (interleukins [ILs], tumor necrosis factors [TNFs], and interferons), eicosanoids (prostaglandins and thromboxanes), reactive oxygen species (O2-, NO, and ONOO-), complements (C3 and C4), and stress hormones (catecholamine, cortisol, vasopressin, and growth hormone). These mediators work to maintain homeostasis under stressful conditions through a complex chain reaction or cascade that results in transient tissue damage known as the inflammatory response. The inflammatory response is decreased by a negative feedback system, which consists not only of the self-inhibitory action of ETX, TNF-alpha, IL-1, and IL-8, but also of the production of antiinflammatory mediators such as IL-4, -10, -11, and -13, TGF-beta, IL-Ra, and sTNFR. If excessive stress or a second attack of stress results in a higher level of inflammation-producing mediators than of inflammation-inhibiting mediators, tissue destruction occurs due to activation and infiltration of inflammatory cells or necrosis due to endothelial injury is seen, followed by disruption of homeostasis, organ dysfunction, and organ failure (multiple organ dysfunction syndrome [MODS] or multiple organ failure [MOF] induced by SIRS). In experimental liver dysfunction after 95% hepatectomy, massive apoptosis of hepatocytes is induced by prolonged hypercytokinemia, ONOO- production, decreased mitochondrial membrane potential of hepatocytes, and decreased Bc12 levels. On the other hand, if the antiinflammatory response is greater than the inflammatory response (CARS) a compromised state and refractory infection are seen, followed by progressive, irreversible organ dysfunction (MODS or MOF induced by CARS).
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PMID:[Inflammatory mediator and organ dysfunction syndrome]. 978 83

The relation between the immune and neuroendocrine response during surgery was studied. In 18 patients undergoing major vascular surgery, circulating interleukin (IL)-1beta and ex-vivo production of IL-1beta and tumour necrosis factor (TNF)-alpha were lower on day 1 after surgery compared to pre-operation values (-14+/-5%, P<0.05; -62+/-9%, P<0.05; and -31+/-54%, P<0.005, respectively). Circulating IL-1 receptor antagonist (IL-1ra) was higher on the 5th day post-operatively compared to pre-operation values (mean +640%+/-400, P<0.05). In a more detailed study in six patients, the ex-vivo production of IL-1beta and TNF-alpha started to decrease at induction of general anaesthesia and dropped to under 10% of initial values at the end of surgery. Circulating IL-1ra and ex-vivo production of IL-1ra started to increase at the end of surgery and remained elevated up to 6 days post-operatively. Plasma antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH) increased during surgery, but cortisol remained unchanged. We demonstrate a depression of circulating pro-inflammatory IL-1beta and an increase of circulating anti-inflammatory IL-1ra during surgical stress. The ex-vivo production of IL-1beta and TNF-alpha was suppressed, indicating a downregulation of the production of these cytokines. This parallelled the hormonal reaction with high ADH and ACTH, but not of cortisol, suggesting that glucocorticoid is not the key-factor in downregulation of production and release of pro-inflammatory cytokines.
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PMID:Depression of plasma levels of cytokines and ex-vivo cytokine production in relation to the activity of the pituitary-adrenal axis, in patients undergoing major vascular surgery. 1032 78

The important neuroendocrine systems implicated in heart failure are reviewed here, with special emphasis on their possible role in pathophysiology and the chances of pharmacological intervention. The part played by the sympathetic nervous system and the renin-angiotensin-aldosterone system and the beneficial effects of beta-blockers, ACE inhibitors, and angiotensin II antagonists are well-established. The involvement of vasopressin, endothelin-1, ANP, BNP, and TNF-alpha and the interventional possibilities relating to these hormones are also discussed. It is concluded that, in addition to the known interventional principles of neuroendocrine activation, there is a series of new exciting principles and some of them might become important in the future.
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PMID:[Neuroendocrine activation in heart failure I. Pathophysiology and pharmacological intervention]. 1109 49

Neurohumoral systems activated in heart failure are reviewed in relation to prognostic and diagnostic information. Plasma levels of noradrenaline, renin, vasopressin, endothelin-1, ANP, BNP, and TNF-alpha are all elevated in heart failure. Most of these factors correlate with the prognosis, but only a minor part seems to possess additional, independent information when other information that is normally available in such patients is taken into account. At present, the diagnosis of heart failure cannot be made on only one blood sample. However, neuroendocrine markers seem: 1) to have a role in the diagnosis and classification of heart failure, 2) to be useful in providing a "neuroendocrine profile", which elucidates different aspects of heart failure, and 3) to be of probable value in the choice and titration of medical treatment for the individual patient in the future.
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PMID:[Neuroendocrine activation in heart insufficiency II. Can diagnosis be confirmed and prognosis evaluated by a blood test?]. 1109 50

Signaling via release of Ca2+ from intracellular stores is mediated by several systems, including the inositol 1,4,5-trisphosphate (IP3) and cADP-ribose (cADPR) pathway. We recently discovered a high capacity for cADPR synthesis in rat glomeruli and cultured mesangial cells (MC). We sought to determine whether 1) cADPR synthesis in MC is regulated by cytokines and hormones, 2) ryanodine receptors (RyRs) are expressed in MC, and 3) Ca2+ is released through RyRs in response to cADPR. We found that ADP-ribosyl cyclase, a CD38-like enzyme that catalyzes cADPR synthesis, is upregulated in MC by tumor necrosis factor-alpha, interleukin-1beta, and all-trans retinoic acid (atRA). [3H]ryanodine binds to microsomal fractions from MC with high affinity in a Ca2+-dependent manner; binding is enhanced by specific RyR agonists and blocked by ruthenium red and cADPR. Western blot analysis confirmed the presence of RyR in MC. Release of 45Ca2+ from MC microsomes was stimulated by cADPR; release was blocked by ruthenium red and 8-bromo-cADPR. ADPR (non-cyclic) was without effect. In MC, TNF-alpha and atRA amplified the increment of cytoplasmic Ca2+ elicited by vasopressin. We conclude that MC possess elements of a novel ADP-ribosyl cyclase-->cADPR-->RyR-->Ca2+-release signaling pathway subject to regulation by proinflammatory cytokines and steroid superfamily hormones.
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PMID:cADP-ribose/ryanodine channel/Ca2+-release signal transduction pathway in mesangial cells. 1139 50

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.
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PMID:Recent developments in the treatment of sepsis. 1255 10

Endotoxin is considered to be a systemic (immunological) stressor eliciting a prolonged activation of the hypothalamo-pituitary-adrenal (HPA) axis. The HPA-axis response after an endotoxin challenge is mainly due to released cytokines (IL-1, IL-6 and TNF-alpha) from stimulated peripheral immune cells, which in turn stimulate different levels of the HPA axis. Controversy exists regarding the main locus of action of endotoxin on glucocorticoid secretion, since the effect of endotoxin on this neuro-endocrine axis has been observed in intact animals and after ablation of the hypothalamus; however, a lack of LPS effect has been described at both pituitary and adrenocortical levels. The resulting increase in adrenal glucocorticoids has well-documented inhibitory effects on the inflammatory process and on inflammatory cytokine release. Therefore, immune activation of the adrenal gland by endotoxin is thought to occur by cytokine stimulation of corticosteroid-releasing hormone (CRH) production in the median eminence of the hypothalamus, which, in turn stimulates the secretion of ACTH from the pituitary. Acute administration of endotoxin stimulates ACTH and cortisol secretion and the release of CRH and vasopressin (AVP) in the hypophysial portal blood. During repeated endotoxemia, tolerance of both immune and HPA function develops, with a crucial role for glucocorticoids in the modulation of the HPA axis. A single exposure to a high dose of LPS can induce a long-lasting state of tolerance to a second exposure of LPS, affecting the response of plasma TNF-alpha and HPA hormones. Although there are gender differences in the HPA response to endotoxin and IL-1, these responses are enhanced by castration and attenuated by androgen and estrogen replacement. Estrogens attenuate the endotoxin-induced stimulation of IL-6, TNF-alpha and IL-1ra release and subsequent activation in postmenopausal women. There appears to be a temporal and functional relation between the HPA-axis response to endotoxin and nitric oxide formation in the neuro-endocrine hypothalamus, suggesting a stimulatory role for nitric oxide in modulating the HPA response to immune challenges.
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PMID:Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis. 1269 14

The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-alpha) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH(1) and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders.
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PMID:Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. 1583 32

It has been shown that stress changes stimulated pro-inflammatory cytokine production and the sensitivity of stimulated cytokine production to glucocorticoid suppression. While glucocorticoid secretion habituates in response repeated stimulation, it is not known whether stimulation and suppression of cytokine production are also subject to adaptation. Eight healthy young subjects were exposed to repeated nauseogenic body rotation on four consecutive days. On each day subjects were rotated around the vertical axis up to five times for a period of 1 min or until subjects chose to stop due to nausea. Blood and saliva samples were obtained before and after rotation for assessment of cortisol, ACTH, plasma vasopressin (ADH), in vitro TNF-alpha and IL-6 production and glucocorticoid sensitivity of TNF-alpha and IL-6 production. Rotation induced increases of ACTH, cortisol, and ADH in the first session. All endocrine responses habituated over time, except for the free cortisol response in men. Pro-inflammatory cytokine production showed a sex-specific response pattern with increases in men and decreases in women in the first session vs. increases in men and women in the last session. Response patterns of GC sensitivity also changed over time: in the first session, sensitivity increased only in men, but in the last session, GC sensitivity decreased in all subjects. In conclusion, in response to repeated nausea induction, habituation occurs only in the endocrine system and predominantly in women. In the immune system, response patterns change in the favor of inflammatory conditions, with increases in stimulated IL-6 and TNF-alpha and decreases in the effectiveness of glucocorticoid suppression of these cytokines. These presumably unfavorable changes in the inflammatory system are more pronounced men.
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PMID:Sex-specific adaptation of endocrine and inflammatory responses to repeated nauseogenic body rotation. 1614 52


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