UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in rabbit sleep-wake activity, brain temperature (Tbr), and behavior were studied after intracerebroventricular injections of a putative endogenous antipyretic, alpha-melanocyte-stimulating hormone (alpha-MSH), and of an endogenous pyrogen, interleukin 1 (IL 1-beta). alpha-MSH (0.1-50.0 micrograms) dose dependently increased wakefulness (W) and decreased Tbr, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). NREMS was more sensitive than REMS to the suppressive effects of low alpha-MSH doses. EEG slow-wave activity in NREMS decreased after alpha-MSH treatment. alpha-MSH elicited stretching, yawning, and signs of sexual excitation. IL 1 (20 and 40 ng) induced fever and excess NREMS. alpha-MSH administered 30 min after IL 1 (40 or 20 ng IL 1 + 0.1, 0.5, or 5.0 micrograms alpha-MSH) significantly attenuated IL 1-induced fever and excess NREMS. IL 1 failed to alter the behavioral effects of alpha-MSH. Despite alpha-MSHs effect on rabbit behavior, total motor activity time did not increase, indicating that increased W after alpha-MSH cannot be attributed to behavioral activation. These results suggest that, besides acting as an endogenous antipyretic, alpha-MSH might be involved in regulation of IL 1-induced sleep.
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PMID:Effects of alpha-MSH on sleep, behavior, and brain temperature: interactions with IL 1. 284 24

An increasing amount of data supports the hypothesis that there are bidirectional circuits between the central nervous system (CNS) and the immune system. Soluble products that appear to transmit information from the immune compartment to the CNS include thymosins, lymphokines, and certain complement proteins. Opioid peptides, adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH) are additional products of lymphocytes that may function in immunomodulatory neuroendocrine circuits. It is proposed that the term "immunotransmitter" be used to describe molecules that are produced predominantly by cells that comprise the immune system but that transmit specific signals and information to neurons and other cell types. Examples would include thymosin alpha 1 and beta 4, lymphocyte-derived ACTH, TSH, and beta-endorphin, interleukin 1, interferon as well as certain other lymphokines and cytokines. The evidence that certain thymosin peptides can serve as immunotransmitters by modulating the hypothalamic-pituitary-adrenal and gonadal axes will be discussed.
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PMID:Evidence that thymosins and other biologic response modifiers can function as neuroactive immunotransmitters. 286 Dec 35

Corticotropin (ACTH) secretion by the anterior pituitary is stimulated by catecholamines in vivo and in vitro. The nature of the response in vivo is controversial but appears to be mediated by beta-adrenergic receptors, whereas the response is dependent on alpha-adrenergic receptors in cultured anterior pituitary cells. In the present studies, by using a superfusion technique, we demonstrate that catecholamine stimulation of ACTH release from rat anterior pituitaries changes with time from a predominantly beta-adrenergic-mediated event to a predominantly alpha-adrenergic-mediated event. From 0 to 2 hr after initiating the superfusion, release of ACTH from anterior pituitary glands is stimulated up to 2.4-fold by the beta-adrenergic agonist l-isoproterenol. However, the ACTH secretory response to the alpha-adrenergic agonist l-phenylephrine is less than or equal to 5% of that to l-isoproterenol during the same time period. Beginning 2 hr after the start of the superfusion, the responsiveness to the beta-adrenergic agonist declines, and the response to the alpha-adrenergic agonist increases until, 10 hr after removal, greater than 95% of the catecholamine-inducible ACTH release is mediated by an alpha-adrenergic pathway. The addition of interleukin 1 alone to the medium from the beginning of the superfusion does not modify basal ACTH secretion rates and does not affect the acquisition of the response to phenylephrine. However, the presence of interleukin 1 does allow the maintenance of the full ACTH secretory response to isoproterenol. This effect of interleukin 1 is reversed by an interleukin 1 antagonist. These observations suggest an additional way in which immune regulators might interact with the hypothalamic-pituitary-adrenal axis.
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PMID:Interleukin 1 prevents loss of corticotropic responsiveness to beta-adrenergic stimulation in vitro. 289 92

In summary, 5HT, ACh, NE, E and DA appear to stimulate hypothalamic CRH secretion whereas activation of the GABA/BZD system seems to decrease the responsivity of the CRH neuron to stimulatory neurotransmitters (Fig. 6). Hypothalamic CRH released from the hypothalamic neuron not only activates the HPA axis, but also stimulates the locus coeruleus-norepinephrine system (LC) and the central sympathetic system (CSS). CRH also induces secretion of hypothalamic POMC gene-derived peptides, such as ACTH, beta-EP, alpha-MSH and CLIP. These peptides as well as CRH itself, decrease the responsivity of the CRH neuron to stimulatory inputs. In addition, glucocorticoids restrain the activity of both the CRH neuron and the locus coeruleus and may also inhibit the secretion of POMC gene-derived peptides by the POMC neurons of the arcuate nucleus. Hypothalamic CRH secretion is regulated also by a number of mediators of the immune response, such as IL-1, IL-2, TNF-alpha and PGF2 alpha, PAF and EGF. Although the physiologic significance of this regulation is largely unknown, it is tempting to speculate that cytokines and mediators of inflammation released in vivo may activate the HPA axis to trigger a glucocorticoid-mediated counter-regulatory mechanism to restrain the immune system (Fig. 7). (Formula: see text). Fig. 7. Schematic representation of the interactions between the HPA axis and the immune system. Continuous lines represent stimulatory inputs and interrupted lines represent inhibitory inputs. In conclusion, our in vitro hypothalamic organ culture system allowed us to examine the regulation of CRH secretion in a direct and specific manner. Some of our observations may help with better understanding of the role played by CRH in the complex symptomatology of stress. In making extrapolations and interpretations from the in vitro data, however, we should try to keep in mind the words of Claude Bernard, "... If we break up a living organism by isolating its different parts it is only for the sake of ease in analysis and by no means in order to consider them separately. Indeed when we wish to ascribe to a physiological quality its value and true significance we must always refer it to this whole and draw our final conclusions only in relation to the effects in the whole".
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PMID:Regulation of rat hypothalamic corticotropin-releasing hormone secretion in vitro: potential clinical implications. 290 18

The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide alpha-melanocyte-stimulating hormone (alpha MSH). The minimal effective concentration of alpha MSH was 10(-11) M. Maximal effect occurred between 10(-8) and 10(-7) M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by alpha MSH with a biphasic dose response. The minimal effective concentration was 10(-11) M, and maximum effect was achieved at 10(-10) M. alpha MSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by alpha MSH. An analog of alpha MSH (Nle4, D-Phe7 alpha MSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of alpha MSH may not be mediated by the classic melanocyte alpha MSH receptor. The influence of alpha MSH on thymocytes and fibroblasts suggests that alpha MSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.
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PMID:Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. 348 61

The ability of i.v.-administered recombinant human interleukin 1 (IL 1 beta) to increase core body temperature, stimulate an increased production of serum amyloid P substance, and augment blood levels of circulating neutrophils in mice was inhibited in a dosage-dependent manner by administration of the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH). alpha-MSH administration was also capable of inhibiting the capacity of i.v.-administered IL 1 beta to enhance plasma levels of corticosterone and to depress the generation and/or elicitation of contact hypersensitivity responses to skin-reactive chemicals. An analog of alpha-MSH (Nle4, D-Phe7 alpha-MSH), known to be more potent than native alpha-MSH in a number of melanotropin-sensitive systems, was determined to be more active than alpha-MSH in the modification of these same in vivo responses. Neither alpha-MSH nor its analog were capable of altering the capacity of IL 1 to stimulate increased plasma levels in prostaglandin E2 (PGE2). In vitro, neither alpha-MSH nor its analog were capable of reducing the capacity of IL 1 to stimulate fibroblast production of PGE2 or to augment the proliferation of murine thymocytes exposed to phytohemagglutinin. The apparent selectivity associated with the regulatory influences of alpha-MSH on IL 1-induced responses in vivo suggests that this neuropeptide may function as an endogenous inhibitor of certain immunomodulatory and inflammatory activities of the cytokine IL 1.
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PMID:Alpha-melanocyte-stimulating hormone exhibits target cell selectivity in its capacity to affect interleukin 1-inducible responses in vivo and in vitro. 349 95

alpha-MSH within the septal region of the brain has been implicated in fever control; this peptide and ACTH (1-24), which contains the alpha-MSH amino acid sequence, reduce fever when given intracerebroventricularly (ICV) or peripherally. These peptides also cause hypothermia when given in doses larger than those required to reduce fever. Both peptides occur naturally within the preoptic PO region of the brain, the CNS locus of primary temperature control. alpha-MSH (350 ng) injected bilaterally into the PO region via chronic cannulas reduced fever caused in six rabbits by IV injection of IL-1 (interleukin 1, endogenous or leukocyte pyrogen) but had no effect in afebrile animals. A larger dose (1.5 micrograms) not only reduced fever but caused hypothermia in 12 rabbits. In separate experiments PO injections of ACTH (1-24) (1 microgram) reduced normal temperature. In the same six rabbits alpha-MSH (1 microgram) caused slightly smaller hypothermia. alpha-MSH (1.5 micrograms) also had no effect in 8 afebrile rabbits when injected into the septum. The primary conclusion is that alpha-MSH receptors within the PO region can contribute to both the antipyretic and hypothermic actions that are observed after ICV and peripheral administration of the peptide.
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PMID:Effects of preoptic microinjections of alpha-MSH on fever and normal temperature control in rabbits. 360 19

Numerous studies have shown that interleukin 1 (IL1), a cytokine secreted by macrophages, is capable of stimulating the hypothalamo-pituitary-adrenal (HPA) axis. Nevertheless, the sites involved in IL1 stimulation of the HPA axis remain, to date, subjects of controversy. In the present study, using in vivo and in vitro approaches, we tried to characterize the route by which IL1 acts on the HPA axis. In vivo, after an i.p. injection of human IL1 beta (1 microgram/rat), we measured plasma ACTH concentration, anterior pituitary (AP) ACTH content, hypothalamic (HT) corticotropin releasing factor (CRF) content, and also AP pro-opiomelanocortin (POMC) and HT CRF gene expression. ACTH and CRF were measured by specific radioimmunoassays (RIAs), and solution hybridization nuclease protection assay was used for quantification of nuclear POMC precursor RNA and nuclear and cytoplasmic POMC and CRF mRNA. Human IL1 beta provoked an increase in ACTH plasma concentration, a decrease in AP ACTH content, and a prolonged increase in AP POMC primary transcript levels (around 100%). A significant increase in AP POMC primary transcript content was evident 30 min after injection of hIL1 beta, while cytoplasmic POMC mRNA levels were increased in the AP only at 4 hr after injection of hIL1 beta. We did not observe an effect of hIL1 beta on either HT CRF content or HT CRF cytoplasmic mRNA levels. In order to characterize a possible direct effect of hIL1 beta at the AP level, we used an AP perifusion system to analyse the effect of hIL1 beta and CRH on ACTH release and on POMC gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human interleukin 1 beta: corticotropin releasing factor and ACTH release and gene expression in the male rat: in vivo and in vitro studies. 751 72

Interleukin-1 beta (IL-1 beta) has been shown to specifically increase the release of prostaglandin (PG) E2 from rat hypothalamic explants in short-term experiments. In this study we attempted to characterize the receptor subtype(s) involved in this response. Rat hypothalamic explants were incubated with mouse monoclonal antibodies (mAbs) raised against human IL-1 type I or type II receptors, IL-1 receptor antagonist (IL-1ra) and alpha-melanocyte-stimulating hormone (alpha-MSH) (which appears to antagonize certain IL-1 induced inflammatory effects in vivo), alone and in the presence of IL-1 beta. PGE2 released into the incubation medium was measured by radioimmunoassay. The anti-type I mAb reduced both basal and IL-1 beta-stimulated PGE2 release at 10 micrograms/ml, but not at lower concentrations. The anti-type II mAb also produced a significant decrease in stimulated release but had no effect on basal release. IL-1ra mimicked the effects of the anti-type I mAb, while alpha-MSH failed to alter either basal or stimulated PGE2 release. These findings suggest that IL-1 beta controls production and release of PGE2 by the rat hypothalamus via both type I and type II receptors, although the latter appear to be involved only in the response to high levels of IL-1.
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PMID:Evidence that the interleukin-1 beta-induced prostaglandin E2 release from rat hypothalamus is mediated by type I and type II interleukin-1 receptors. 759 52

The results described herein indicate that elevation of IL-1 in rat brain, either by infusion of IL-1 into the brain or by stimulation of release of endogenous IL-1 in the brain by LPS, rapidly suppresses a variety of immune responses measured in peripheral lymphocytes. This effect can be blocked by infusion of alpha-MSH into brain, an attribute that was used to indicate that the effects of LPS infusion occurred by stimulation of endogenous IL-1 and not some other influence of LPS. That suppression of cellular immune responses indeed describes the consequences of elevating IL-1 in brain was shown by determining the time course of effects and thereby demonstrating that rebound enhancement of cellular immune responses did not occur after either IL-1 or LPS. Studies that examined the mechanisms by which brain IL-1 affects immune responses indicated that IL-1 influences peripheral lymphocytes by stimulation of CRF in the central nervous system and that CRF in turn causes suppression of cellular immune responses through activation of both the pituitary-adrenal axis and the autonomic nervous system. These findings have also been observed in another laboratory. Moreover, Brown et al. have shown that IL-1 in brain suppresses macrophage function in addition to the suppression of lymphocyte functions described herein. The physiologic significance of IL-1 actions in the brain on immune responses remains to be determined, but the demonstration that this cytokine influences immune processes by acting in brain opens for study another means by which brain and immune system interact.
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PMID:Widespread activation and consequences of interleukin-1 in the brain. 782 22

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