Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the effects of experimental lead pollution on gut endocrine cells have been determined in the goldfish Carassius carassius (L.) var.auratus by immunocytochemical reactions. In the mucosa and submucosa, only vasoactive intestinal polypeptide- and 5-HT-like immunoreactive nerve fibers were observed. Endocrine cells displaying immunoreactivity against gastrin, CCK8, metenkephalin, bombesin, neuropeptide Y, pancreatic polypeptide, substance P, secretin, somatostatin and vasoactive intestinal polypeptide antibodies were detected. No immunoreactivity against glucagon, insulin and 5-HT antibodies was revealed in the endocrine cells. Some modifications appeared evident in the endocrine cells 48-96 h after lead intoxication, and can be summarized as follows: 1) discharge of secretory granules (secretin- and vasoactive intestinal polypeptide-like peptides), up to the extent that the cells appeared to be depleted of secretory material; 2) increase of immunoreactivity in the endocrine cells (met-enkephalin- and pancreatic polypeptide-like peptides) or in the frequency of positive cells (met-enkephalin-like peptide); 3) no variations (gastrin-, CCK8, bombesin-, somatostatin- and substance P-like peptides). The alterations were not enhanced by long term treatment. Nerve fibers did not show modifications.
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PMID:Immunocytochemical study of endocrine cells in the gut of goldfish Carassius carassius (L.) var. auratus submitted to experimental lead intoxication. 911 38

The mechanisms underlying inflammatory bowel disease (IBD) remain obscure but the importance of inflammatory processes is clear and most pharmacological therapies inhibit inflammation. The search for more effective agents with low toxicity continues. To test the possibility that the antiinflammatory/anticytokine peptide alpha-MSH can be used to control IBD, the peptide was administered to a murine colitis model. The peptide treatment had marked salutary effects: it reduced the appearance of fecal blood by over 80%, inhibited weight loss, and prevented disintegration of the general condition of the animals. Mice given alpha-MSH showed markedly lower production of TNF alpha by tissues of the lower colon stimulated with concanavalin A; the inhibitory effect of alpha-MSH on production of inflammatory nitric oxide by lower bowel tissue was even greater. The combined results indicate that alpha-MSH modulates experimental IBD, perhaps by inhibiting production within the gut of the local proinflammatory agents TNF alpha and nitric oxide, or by inhibiting inflammatory processes closely linked to these mediators.
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PMID:alpha-MSH modulates experimental inflammatory bowel disease. 914 24

Hemorrhage is associated with an impairment in the immune response and with increased concentrations of circulating inflammatory cytokines. The present study determined the time course and localization of alterations in circulating and tissue pro-inflammatory cytokines (TNF-alpha, IL-1-alpha and -beta) in response to fixed-pressure (40 mm Hg) hemorrhage as well as the associated hanges in circulating neurohormonal and opioid mediators. Conscious unrestrained non-heparinized male Sprague-Dawley rats (n = 24) underwent hemorrhage followed by standard resuscitation with lactated Ringer's solution. Animals were sacrificed at three time points; immediately after the hemorrhage period, at completion of resuscitation and 1.5 h after the resuscitation period. Hemorrhage resulted in marked elevations in circulating levels of TNF-alpha, which averaged 860 +/- 201 pg/ml. The levels were similarly elevated following fluid resuscitation (877 +/- 196 pg/ml) and had decreased towards baseline 1.5 h after completion of resuscitation (281 +/- 134 pg/ml). TNF-alpha was not detectable in plasma of time-matched controls. Hemorrhage elevated TNF-alpha content in spleen (25%), lung (55%) and heart (20%), and tissue content remained elevated despite resuscitation. No significant changes in tissue content of TNF-alpha were detected in the liver, kidney or brain. Circulating levels of IL1-alpha and -beta were not detectable in either the time-matched controls or hemorrhaged animals. However, statistically significant elevations in tissue content of IL-1 alpha were observed in heart, spleen, lung, gut and whole brain (15-30%). Tissue content of IL-1 beta did not change in response to hemorrhage and/or fluid resuscitation. Activation of sympathetic outflow, as evidenced by a 3- to 4-fold elevation in circulating epinephrine and norepinephrine levels, was observed immediately after hemorrhage, and was associated with a 5-fold rise in circulating beta-endorphin. These results demonstrate an early increase in tissue cytokine content following hemorrhagic shock, which is associated with elevations in circulating catecholamines and endogenous opioids, consistent with their potential modulatory role in this response.
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PMID:Early organ-specific hemorrhage-induced increases in tissue cytokine content: associated neurohormonal and opioid alterations. 932 42

Samples of oesophagus, first, second and third stomach, duodenal ampulla, proximal intestine and distal intestine including rectum were obtained from striped dolphins (Stenella coeruleoalba) stranded along Italian coasts, fixed in formalin and used for immunohistochemistry. The possible presence of neuropeptides and the biogenic amine serotonin was investigated by a labelled streptavidin-biotin method. Neuropeptide Y (NPY)-, substance P-, calcitonin gene-related peptide (CGRP)-, metenkephalin-, gastrin releasing peptide (GRP)/bombesin-, and somatostatin-like immunoreactivities were present in the submucosal as well as the myenteric plexuses, even with differences of distribution in the various organs. Vasoactive intestinal poly-peptide (VIP)-like immunoreactivity was detected in the submucosal plexus, whereas beta-endorphin- and leu-enkephalin-like immunoreactivities were shown in the myenteric plexus only. NPY-, substance P-, CGRP- and VIP-like-immunoreactivities were also observed in perivascular nerve fibres. In addition, VIP-, GRP- and somatostatin-like immunoreactivities were detected in myelinated nervous bundles. These were localized in the submucosal and muscular layers all along the gastrointestinal tract, and possibly sustain an exceptionally rapid response of the target structures. It is note-worthy that peptidergic axons in the wall of the gut of the majority of mammals are unmyelinated. A somatostatin-like peptide was identified in epithelial cells only in the second stomach, whereas in terrestrial mammals this endocrine cell type occurs widely. Immunoreactivity to serotonin was never detected, and this is a further difference in comparison with the majority of other mammals.
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PMID:Localization of regulatory peptides in the gastrointestinal tract of the striped dolphin, Stenella coeruleoalba (Mammalia: Cetacea). An immunohistochemical study. 949 15

The regulation of body fat stores is a problem of energy and nutrient balance that can be most readily viewed as a feedback system. Several elements are involved in any feedback system, including afferent signals, a controller that senses the afferent signals and transduces their information and then activates efferent controls that regulate the controlled system. The recent discovery of leptin has provided a major missing link in the feedback control system. This afferent signal is produced exclusively in fat cells of nonpregnant mammals but can be produced in the placenta as well. This circulating peptide has a very strong relationship to the level of body fat and its absence experimentally and clinically produces massive obesity. In the controller, or brain, several anatomic regions play a central role in regulating fat stores. Damage to the ventromedial nucleus (VMH) or the paraventricular nucleus (PVN) in the hypothalamus produces massive obesity in mammals and birds. Injury to the central nucleus of the amygala will also produce obesity. In contrast, damage to the lateral hypothalamus reduces body fat. The syndrome of leptin deficiency or defects in the leptin receptors produce a massive obesity that is metabolically similar to the VMH or PVN lesion syndromes of obesity, suggesting that leptin may have its metabolic effects through these medial hypothalamic centers. Support for this idea has come from studies showing that damage to the PVN or VMH will block the effects of leptin. A number of neuropeptides and monoamines are involved with modulating of food intake and fat stores. Both serotonin, acting through 5-HT2C receptors, and norepinephrine, acting through beta 2 and/or beta 3 receptors, reduce food intake. A variety of peptides also influence food intake and body fat. Neuropeptide Y, dynorphin, galanin, and melanocyte-stimulating hormone all increase food intake. In contrast, a large number of peptides--including cholecystokinin, corticotrophin-releasing hormone/urocortin, enterostatin, insulin, leptin, alpha-MSH, and TRH--reduce food intake. Chronic administration of neuropeptide Y, acting through Y-5 receptors, can produce chronically increased food intake and obesity. This syndrome is similar to the VMH syndrome and suggests that NPY must be acting as an inhibitor of a feeding system. The melanocortin receptor system may be particularly important because a mouse that does not express MC4 receptors is massively overweight. These central systems modulate food intake and fat stores by the controlled system. Glucocorticoids from the adrenal gland are important in obesity, since adrenalectomy will reverse or prevent the development of all forms of obesity. The sympathetic nervous system is also important because low sympathetic activity is associated with experimental and clinical obesity. The reciprocal relationship between food intake and sympathetic activity has been a robust relationship, suggesting that beta receptors in the periphery or brain may be involved in feeding control. In one model of dietary obesity resulting when animals eat a high-fat diet, the syndrome is blocked by inhibitory adrenal steroid activity. These animals show a lower level of sympathetic activity and a low level of brain serotonin. Finally, they show an enhanced sensitivity to essential fatty acids when these are applied to the tongue or given into the gut. In this chapter, the control of energy stores as fat is viewed as a feedback system. Leptin is perceived as a key afferent signal and glucocorticoids and the sympathetic nervous system through beta receptors as essential elements of this control system.
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PMID:The MONA LISA hypothesis in the time of leptin. 976 5

Crib-biting in the horse is frequently prevented in the short-term by horse-owners using physical means. Because it has been proposed that crib-biting may function to reduce stress, the effect of prevention of crib-biting and/or eating on the behaviour, heart rate, and plasma cortisol and beta-endorphin concentrations was measured in six crib-biting and six normal horses. When crib-biters were unable to crib-bite, they showed an increase in ingestive behaviour. When crib-biters were prevented from crib-biting and eating, a relative stasis in the motility of the foregut occurred, suggesting that normal gut function in these animals depends on ad libitum access to food and to suitable crib-biting substrates. There was no significant difference in the mean baseline levels of normal and crib-biting horses but, contrary to expectations, beta-endorphin levels were higher in crib-biting horses than in normal horses when crib-biting was prevented. Mean baseline levels of cortisol were higher, under a variety of test and control conditions, in crib-biting than in normal horses, but there was no significant rise in cortisol levels in crib-biters during periods when crib-biting was prevented, suggesting that the function of this oral stereotypy does not lie in stress-reduction.
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PMID:Physiological and behavioral consequences associated with short-term prevention of crib-biting in horses. 981 60

Pancreatic polypeptide (PP) is a member of a family of 36-amino acid brain-gut peptides, including neuropeptide Y (NPY) and polypeptide YY (PYY) and acting through many subtypes of Y receptors belonging to the superfamily of the G protein-coupled receptors. PP was found to increase both glucocorticoid and cyclic-AMP production by dispersed rat and human adrenocortical cells in a concentration-dependent manner. Minimal and maximal effective concentrations were 10(-10) and 10(-8) M, respectively. The glucocorticoid secretagogue effect of 10(-8) M PP was blocked by the protein kinase A (PKA) unhibitor H-89, but not by the ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP) Autoradiography showed the presence of [125I]PP binding sites in the inner zones of rat and human adrenal cortex, which were not displaced by NPY, PYY, ACTH or CIP. Sizable amounts of PP-immunoreactivity were detected in the medulla of both rat and human adrenals (about 50-100 fmol/mg); this content may give rise, upon submaximal stimulation of PP release, to local intraadrenal concentrations of about 10(-8)/10(-7) M. Collectively, these findings allow us to draw the following conclusions: (i) PP stimulates glucocorticoid secretion, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway; and (ii) PP could be included in that group of regulatory peptides, contained in adrenal medulla, which are able to control the secretory function of the cortex acting in a paracrine manner.
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PMID:The possible involvement of pancreatic polypeptide in the paracrine regulation of human and rat adrenal cortex. 988 61

Endogenous opioid peptides - enkephalins, beta-endorphin and dynorphins - are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists - morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide - have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials.
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PMID:Role of opioid ligands in the irritable bowel syndrome. 1020 12

The presence of the ancient anti-inflammatory peptide alpha-melanocyte-stimulating hormone [alpha-MSH (1-13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. alpha-MSH and and its carboxy-terminal tripeptide (11-13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. alpha-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of alpha-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of alpha-MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of alpha-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because alpha-MSH has potent anti-inflammatory effects we determined influences of alpha-MSH on C. albicans and S. aureus killing by human neutrophils. alpha-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. alpha-MSH peptides that combine antipyretic, anti-inflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist.
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PMID:Antimicrobial effects of alpha-MSH peptides. 1909 31

The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of 'feeding' and 'satiety' centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. Antagonists of the Y5 receptor (currently thought to be the NPY 'feeding' receptor) have anti-obesity effects. Melanocortin-4 receptors (MC4-R) are expressed in various hypothalamic regions, including the ventromedial nucleus and ARC. Activation of MC4-R by agonists such as alpha-melanocyte-stimulating hormone (a cleavage product of pro-opiomelanocortin which is expressed in ARC neurones) inhibits feeding and causes weight loss. Conversely, MC4-R antagonists such as 'agouti' protein and agouti gene-related peptide (AGRP) stimulate feeding and cause obesity. Ectopic expression of agouti in the hypothalamus leads to obesity in the AVY mouse, while AGRP is co-expressed by NPY neurones in the ARC. Synthetic MC4-R agonists may ultimately find use as anti-obesity drugs in human subjects Orexins-A and -B, derived from prepro-orexin, are expressed in specific neurones of the lateral hypothalamic area (LHA). Orexin-A injected centrally stimulates eating and prepro-orexin mRNA is up regulated by fasting and hypoglycaemia. The LHA is important in receiving sensory signals from the gut and liver, and in sensing glucose, and orexin neurones may be involved in stimulating feeding in response to falls in plasma glucose.
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PMID:The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box. 1099 54


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