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)

During infection, bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These cytokines can reach the brain by several routes. Furthermore, cytokines, such as interleukin-1 (IL-1), are induced in neurons within the brain by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion that characterizes infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing hormone-releasing hormone (LHRH) from LHRH neurons, thereby blocking pulsatile LH but not follicle-stimulating hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH. IL-1 alpha and granulocyte macrophage colony-stimulating factor (GMCSF) block the response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit LHRH release is as follows. It acts on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone (GHRH) release, which is mediated by NO, and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of PRL release is also mediated by intrahypothlamic action of NO, which inhibits release of the PRL-inhibiting hormone dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase-liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase (COX) and lipoxygenase (LOX) with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part via induction of inducible NOS. The NO produced inhibits release of ACTH. The adipocyte hormone leptin, a member of the cytokine family, has largely opposite actions to those of the proinflammatory cytokines, stimulating the release of FSHRF and LHRH from the hypothalamus and FSH and LH from the pituitary directly by NO.
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PMID:The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection. 1126 67

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.
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PMID:COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production. 1183 69

Nicotine is a potent stimulus for the hypothalamic-pituitary-adrenal (HPA) axis. Systemic nicotine acts via central mechanisms to stimulate by multiple pathways the release of ACTH from the anterior pituitary corticotrops and corticosterone from the adrenal cortex. Nicotine may stimulate indirectly the hypothalamic paraventricular nucleus, the site of the corticotropin-releasing hormone (CRH) neurons which activates ACTH release. In the present studies an involvement of adrenergic system and prostaglandins synthesized by constitutive cyclooxygenase (COX-1) and inducible cyclooxygenase (COX-2) in the nicotine-induced HPA response in rats was investigated. Nicotine (2.5-5 mg/kg i.p.) significantly increased plasma ACTH and corticosterone levels measured 1 hr after administration. Adrenergic receptor antagonists or COX inhibitors were injected i.p. 15 min prior to nicotine and the rats were decapitated 1 hr after the last injection. Prazosin (0.01-0.1 mg/kg), an alpha1-adrenergic antagonist, significantly decreased the nicotine-evoked ACTH and corticosterone secretion. Yohimbine (0.1-1.0 mg/kg), an alpha2-adrenergic antagonist, moderately diminished ACTH response, and propranolol (0.1-10 mg/kg), a beta-adrenergic antagonist, did not significantly alter the nicotine-induced hormones secretion. Pretreatment with piroxicam (0.2-2.0 mg/kg), a COX-1 inhibitor, considerably impaired the nicotine-induced ACTH and corticosterone secretion. Compound NS-398 (0.2-5.0 mg/kg), a selective COX-2 blocker did not markedly alter these hormones secretion, and indomethacin (2 mg/kg), a non-selective COX inhibitor significantly diminished ACTH response. These results indicate that systemic nicotine stimulates the HPA axis indirectly, and both adrenergic system and prostaglandins are significantly involved in this stimulation. Noradrenaline, stimulating postsynaptic alpha1-adrenergic receptors, and prostaglandins, synthesized by COX-1 isoenzyme, are of crucial significance in the nicotine-induced ACTH and corticosterone secretion.
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PMID:Effect of adrenergic antagonists and cyclooxygenase inhibitors on the nicotine-induced hypothalamic-pituitary-adrenocortical activity. 1212 Sep 2

Plasma noradrenaline reflects the release from adrenal medulla and sympathetic nerves; however, the exact mechanisms of adrenal noradrenaline release remain to be elucidated. The present study was designed to characterize the source of plasma noradrenaline induced by centrally administered vasopressin and corticotropin-releasing hormone (CRH) in urethane-anesthetized rats. Intracerebroventricularly administered vasopressin (0.2 nmol/animal) and CRH (1.5 nmol/animal) elevated plasma levels of noradrenaline and adrenaline. Intracerebroventricularly administered indomethacin [1.2 micromol (500 microg)/animal] (an inhibitor of cyclooxygenase) abolished the elevations of both noradrenaline and adrenaline induced by vasopressin and CRH. Intracerebroventricularly administered furegrelate [1.8 micromol (500 microg)/animal] (an inhibitor of thromboxane A(2) synthase) abolished the elevations of both noradrenaline and adrenaline induced by vasopressin, while the reagent only attenuated the elevation of plasma adrenaline evoked by CRH. Acute bilateral adrenalectomy abolished the elevation of both noradrenaline and adrenaline induced by vasopressin, while the procedure reduced only the elevation of adrenaline induced by CRH. These results suggest that the release of noradrenaline from adrenal medulla and sympathetic nerves is mediated by different central mechanisms. The vasopressin-induced noradrenaline release from adrenal medulla is mediated by brain thromboxane A(2)-mediated mechanisms, while the CRH-induced noradrenaline release from sympathetic nerves is mediated by brain prostanoid (other than thromboxane A(2))-mediated mechanisms. The vasopressin- and CRH-induced adrenaline release from adrenal medulla is also mediated by brain thromboxane A(2)-mediated mechanisms in rats.
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PMID:Role of brain thromboxane A2 in the release of noradrenaline and adrenaline from adrenal medulla in rats. 1270 65

Previously, we reported that the elevation of plasma noradrenaline and adrenaline induced by intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) was abolished by i.c.v. administered indomethacin, an inhibitor of cyclooxygenase, in rats [Yokotani et al., Eur. J. Pharmacol. 419, 183-189, 2001]. The result suggests the involvement of active metabolites of brain arachidonic acid in the CRH-induced activation of the central sympatho-adrenomedullary outflow. Arachidonic acid is released mainly by two different pathways: phospholipase A2-dependent pathway; phospholipase C- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we tried to identify which pathway is involved in the CRH-induced elevation of plasma catecholamines in urethane-anesthetized rats. CRH (1.5 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was abolished by neomycin [0.55 micromol (500 microg)/animal, i.c.v.] and 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U-73122) [5 nmol (2.3 microg)/animal, i.c.v.] (inhibitors of phospholipase C), and also by 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267) [1.3 micromol (500 microg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 micromol (500 microg)/animal, i.c.v.] (an inhibitor of phospholipase A2) and 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-2,5-pyrrolidinedione (U-73343) [5 nmol (2.3 microg)/animal, i.c.v.] (an inactive analog of U-73122) had no effect. These results suggest that CRH activates the central sympatho-adrenomedullary outflow by the brain phospholipase C- and diacylglycerol lipase-dependent mechanisms in rats.
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PMID:Brain phospholipase C and diacylglycerol lipase are involved in corticotropin-releasing hormone-induced sympatho-adrenomedullary outflow in rats. 1295 58

Brain nitric oxide (NO), recognized as a neurotransmitter or a neuromodulator, is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. NO has been shown to activate cyclooxygenase (a prostaglandin-forming enzyme) in addition to guanylate cyclase. Recently, we reported that the intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) increases plasma catecholamines through brain cyclooxygenase-dependent mechanisms in rats. In the present experiments, therefore, we examined whether NO is involved in the CRH-induced increase of plasma catecholamines using urethane-anesthetized rats. I.c.v. administered CRH increased plasma noradrenaline and adrenaline in a dose-dependent manner (0.5, 1.5, and 3.0 nmol/animal). The CRH (1.5 nmol/animal, i.c.v.)-induced increase of plasma catecholamines was reduced by N(omega)-nitro-L-arginine methyl ester (a non-selective inhibitor of NOS) [111 nmol (30 microg)/animal, i.c.v.], but not by the same dose of N(omega)-nitro-D-arginine methyl ester (an inactive isomer of N(omega)-nitro-L-arginine methyl ester). The CRH-induced increase of plasma catecholamines was also reduced either by cycloheximide (an inhibitor of protein synthesis) [107 nmol (30 microg)/animal, i.c.v.] or by S-methylisothiourea (an inhibitor of inducible NOS) [71 nmol (20 microg) and 711 nmol (200 microg)/animal, i.c.v.]. These results suggest the involvement of brain inducible NOS in the CRH-induced activation of the central sympatho-adrenomedullary outflow in rats.
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PMID:Inducible nitric oxide synthase is involved in corticotropin-releasing hormone-mediated central sympatho-adrenal outflow in rats. 1451 12

The effect of alpha-MSH on reactive oxygen species (ROS) production by rat peritoneal neutrophils and the effect of cyclooxygenase (COX) inhibition were investigated using the chemiluminescence (CL) technique. Cells were obtained by peritoneal lavage 4h after administration of oyster glycogen to rats and were stimulated with lipopolysaccharide (LPS) from Salmonella enderitidis and phorbol 12-myristate 13-acetate (PMA). The increasing concentrations of alpha-MSH (10(-12)-10(-6) M) were added to stimulated cells alone or along with the COX inhibitors indomethacin, ketorolac or nimesulide (10(-8)-10(-5) M). Luminol and lucigenin CL levels were significantly increased in cells stimulated with LPS and PMA compared to unstimulated ones. alpha-MSH significantly reduced lucigenin CL values and this effect was completely reversed in the presence of indomethacin (10(-8) and 10(-7) M). In conclusion, alpha-MSH inhibits the production of superoxide radicals by activated rat peritoneal neutrophils and COX contributes to this effect.
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PMID:The role of cyclooxygenase inhibition in the effect of alpha-melanocyte-stimulating hormone on reactive oxygen species production by rat peritoneal neutrophils. 1517 77

There is evidence that alpha-melanocyte-stimulating hormone (alpha-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of alpha-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 microg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by alpha-MSH (3 nmol/rat) injected 30 min before LPS. alpha-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of alpha-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of alpha-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by alpha-MSH. Both LPS and alpha-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and alpha-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of alpha-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 microg/ml) and LPS plus interferon-gamma (IFN-gamma, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-gamma. This stimulatory effect was attenuated in the presence of alpha-MSH (5 microM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that alpha-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous alpha-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.
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PMID:Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats. 1521 20

Heme oxygenase (HO) cleaves the tetrapyrrolic ring of cellular heme moieties liberating carbon monoxide (CO) and equimolar amounts of free iron and biliverdin (BV). BV is in turn converted into bilirubin (BR) by the cytosolic enzyme BV reductase. Three HO isoforms have been described to date: HO-1, HO-2, and HO-3. All these isoforms are present in nervous tissue with different localizations and regulation. CO, the gaseous product of HO, exerts its biological effects through the activation of soluble guanylyl cyclase, but alternative signaling pathways, such as the activation of cyclooxygenase, have also been reported in the brain. In vitro and in vivo studies showed that CO, at the hypothalamic level, plays a key role in the modulation of stress response because it inhibits the release of antiinflammatory neuropeptides, such as corticotropin-releasing hormone and arginine vasopressin, and increases body temperature in rodents exposed to psychological stressors (stress fever). In the last few years, a new role of BR as an endogenously produced antioxidant has emerged, and several reports have shown that BR contributes to prevent cell damage mediated by reactive oxygen species, as well as nitric oxide and its congeners.
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PMID:Heme oxygenase and its products in the nervous system. 1534 48

As the distribution of apelinergic neurons in the brain suggests an important role of apelin-13 in the regulation of neuroendocrine processes, in the present experiments the effects of this recently identified neuropeptide on the open-field activity, the hypothalamo-pituitary-adrenal (HPA) system and the body temperature were investigated. I.c.v. administration of apelin-13 (1-10 microg) to rats caused significant increases in square crossing, rearing, plasma corticosterone release and core temperature, whereas it did not influence the spontaneous motor activity during telemetric observation. To determine the mediation of the actions of apelin, a corticotropin-releasing hormone (CRH) antagonist, the nonselective dopamine antagonist haloperidol, the selective dopamine D1 receptor antagonist SCH-23390 and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine-methyl ester (L-NAME) were administered to the rats. The apelin-evoked HPA activation was diminished by preadministration of the CRH antagonist, while the dopamine antagonist and L-NAME attenuated only the square crossing and rearing induced by apelin-13. To characterize the transmission of the thermoregulatory action of apelin, animals were pretreated either with L-NAME, the CRH antagonist or with the cyclooxygenase inhibitor noraminophenazone. L-NAME and the CRH antagonist did not cause significant inhibition of the apelin-evoked increase in core temperature, while the cyclooxygenase inhibitor, applied 30 min before peptide treatment, did not prove effective in preventing the apelin-evoked thermoregulatory response, whereas when it was administered 2 h after the peptide treatment, it transiently and significantly reduced the hyperthermic response. The present data suggest that apelin-13 plays an important role in the regulation of behavioral, endocrine and homeostatic responses in the CNS, and dopamine, nitric oxide and prostaglandins seem to take part in the mediation of its effects. Since the corticosterone response could be blocked by the CRH antagonist, it is likely to be mediated through the activation of the CRH neurons.
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PMID:Behavioral, neuroendocrine and thermoregulatory actions of apelin-13. 1554 2

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