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)

Most neuropeptides are known to occur both in the central nervous system and in blood. This, as well as the occurrence of central nervous peptide effects after peripheral administration, show the importance of studying the relationships between the peptides in the two compartments. For many peptides, such as the enkephalins, TRH, somatostatin and MIF-1, poor penetration of the blood-brain barrier was shown. In other cases, including beta-endorphin and angiotensin, peptides are rapidly degraded during or just after their entry into brain or cerebrospinal fluid. Some peptides, such as insulin, delta-sleep-inducing peptide, and the lipotropin-derived peptides, enter the cerebrospinal fluid to a slight or moderate extent in the intact form. Many peptide hormones, such as insulin, calcitonin and angiotensin, act directly on receptors in the circumventricular organs, where the blood-brain barrier is absent. Oxytocin, vasopressin, MSH, and an MSH-analog alter the properties of the blood-brain barrier, which may result in altered nutritient supply to the brain. In conclusion, the diffusion of most peptides across the brain vascular endothelium seems to be severely restricted. There are, however, several alternative routes for peripheral peptides to act on the central nervous system. The blood-brain barrier is a major obstacle for the development of pharmaceutically useful peptides, as in the case of synthetic enkephalin-analogs.
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PMID:Minireview. Peptides and the blood-brain barrier. 630 42

Substance P (SP) and adrenocorticotropic hormone (ACTH) are peptides that have been shown to have both neurological and immunological effects. Because of the demonstrated effects upon immune function, we examined the effects of these peptides on T-lymphocyte adhesion to vascular endothelium and surface adhesion receptor expression. Neither the adhesion assays nor the expression assays showed any statistically significant effect of SP (10 microM) or ACTH (1 microM) for any incubation period used. We conclude that, while SP and ACTH have a variety of immunomodulatory effects, direct modulation of T-lymphocyte adhesion to vascular endothelium is probably not one of them.
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PMID:Substance P and adrenocorticotropic hormone do not affect T-lymphocyte adhesion to vascular endothelium or surface expression of adhesion receptors. 751 58

To study facial flush after systemic administration of human corticotropin-releasing hormone (hCRH) we injected 100 micrograms hCRH intravenously to ten healthy young men. The increase in facial temperature was measured by infrared camera. A significant increase in facial temperature of 1.39 degrees C +/- 0.3 was found within 7 min in all patients, which lasted up to 60 min, although facial flushing was visible in only 50% (5/10) of the probands. In a second experiment 100 micrograms hCRH was then administered to seven other healthy young men. Intra- and extracerebral blood flow velocity changes in the medial cerebral artery (MCA) and external carotid artery (ECA) were measured after hCRH administration by use of Doppler sonography. We found a decrease of intracerebral blood flow which was caused by hyperventilation and was reversible following 6% CO2 hyperventilation during a second injection of 100 micrograms hCRH. Blood flow velocity in the ECA increased by 111.5 +/- 32.9% (compared to baseline level), lasted up to 60 min after hCRH injection, and was not reversible by 6% end-tidal CO2 ventilation. We thus demonstrated that the direct vasodilatory effect of hCRH involves the ECA-supplied vascular territory only. The intracerebral vasoconstrictory effect represents the result of hyperventilation following hCRH injection. The data thus clearly suggest an interaction of hCRH and the vascular endothelium of the ECA, causing a marked blood flow velocity increase and facial flushing.
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PMID:Intra- and extracerebral blood flow changes and flushing after intravenous injection of human corticotropin-releasing hormone. 808 64

We sought to evaluate the antiinflammatory effects of synthetic human beta-endorphin (SHB) when injected into the canine knee joint. Sixteen healthy dogs, aged 1-2 yr, were selected. SHB was injected pre- and postinjury into each knee. The sample size was n = 32 after a randomized factorial arrangement; 2 x 4 with four cases per treatment being performed. Factors considered were: Factor A with two levels: A1 = Preinjury and A2 = Postinjury; Factor B (SHB dose) with four levels: B1 = Control, B2 = 250 micrograms, B3 = 500 micrograms, B4 = 1000 micrograms. The control group received 0.9% NaCl solution. Anesthesia was induced with intravenous thiopental, 14 mg/kg, and acepromazine, 0.5 mg/kg. Injury was produced with an intraarticular injection of 4 mL HCl 0.5 M, which was left in situ for 20 min. Inflammation was measured using the 610 nm absorbency of Evans blue extravasate in biopsy specimens. Histopathologic studies were performed on each knee. We found that beta-endorphin has a clear, dose-related, antiinflammatory effect, reducing the tissue extravasation of Evans blue and its absorbency, especially with large doses. This finding was consistent with the histopathologic observations. We conclude that SHB has an antiinflammatory effect. It is still not clear which mechanisms inhibit polymorphonuclear cell adhesion to vascular endothelium or cell and plasmatic protein extravasation.
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PMID:An evaluation of the antiinflammatory effects of intraarticular synthetic beta-endorphin in the canine model. 871 98

Opioid-containing immune cells migrate preferentially to inflamed sites, where they release beta-endorphin which activates peripheral opioid receptors to inhibit pain. Immunocyte recruitment is a multistep, sequential engagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasation into inflamed sites. Here we show that anti-selectin treatment abolishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotropin-releasing factor. This results from a blockade of the infiltration of immunocytes containing beta-endorphin and the consequent decrease of the beta-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain is exacerbated by measures inhibiting the immigration of opioid-producing cells or, conversely, analgesia might be conveyed by adhesive interactions that recruit those cells to injured tissue.
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PMID:Pain control in inflammation governed by selectins. 984 66

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.
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PMID:Plasma beta-endorphin and adenosine concentration in pulmonary hypertension. 1075 27

Pain can be effectively controlled by endogenous mechanisms based on neuroimmune interactions. In inflamed tissue immune cell-derived opioid peptides activate opioid receptors on peripheral sensory nerves leading to potent analgesia. This is brought about by a release of opioids from inflammatory cells after stimulation by stress or corticotropin-releasing hormone (CRH). Immunocytes migrate from the circulation to inflamed tissue in multiple steps, including their rolling, adhesion, and transmigration through the vessel wall. This is orchestrated by adhesion molecules on leukocytes and vascular endothelium. Intercellular adhesion molecule-1 [ICAM-1 (or CD54)] is expressed by endothelium and mediates adhesion and extravasation of leukocytes. The goal of this study was to show that ICAM-1 regulates the homing of opioid-producing cells and the subsequent generation of analgesia within sites of painful inflammation. This was accomplished using immunofluorescence, flow cytometry, and behavioral (paw pressure) testing. We found that ICAM-1 is upregulated on the vascular endothelium, simultaneously with an enhanced immigration of opioid-containing immune cells into inflamed paw tissue. The intravenous administration of a monoclonal antibody against ICAM-1 markedly decreased the migration of opioid-containing leukocytes and of granulocytes, monocytes-macrophages, and T cells to the inflamed tissue. At the same time, circulating immunocytes increased in numbers, and macroscopic inflammation (hyperalgesia, paw volume, and paw temperature) remained primarily unchanged. Most importantly, peripheral opioid analgesia elicited either by cold water swim stress or by intraplantar administration of CRH was dramatically reduced. Together, these findings indicate that ICAM-1 expressed on vascular endothelium recruits immunocytes containing opioids to promote the local control of inflammatory pain.
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PMID:Opioid control of inflammatory pain regulated by intercellular adhesion molecule-1. 1209 10

Modulation of locally produced corticotropin-releasing hormone (CRH) is a component of the cytokine network in human inflammatory arthritis. CRH signaling, through the CRH-receptor subtype R1alpha, may play a role in both vascular changes and pathologic mechanisms associated with joint inflammation. Furthermore, the peripheral actions of CRH may be mediated in part through the NURR subfamily of nuclear orphan receptors. The aim of this study was to establish the signaling mechanisms through which CRH receptor-mediated responses contribute to gene regulation in inflamed synovial vasculature. Immunohistochemical analysis of serial rheumatoid arthritis (RA) tissue sections demonstrates CRH and NURR1 expression in the synovial lining layer, subsynovial lining layer, and the vascular endothelium. The identical pattern of immunolocalization confirms that NURR1 is produced at the same synovial sites shown to produce CRH. The distribution of specific NURR1 staining on the synovial vasculature parallels that observed for CRH-R1 expression. Using primary synovial tissue endothelial cells, we demonstrate that CRH induces specific CREB-1 and ATF-2 binding to the NURR1 promoter. We further provide evidence that CRH signaling can be mimicked by activation of cAMP/PKA/CREB using forskolin in primary human microvascular endothelial cells. These data indicate that the CRH receptor-dependent inflammatory response in synovial tissue endothelium is mediated through the cAMP/CREB signaling pathway.
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PMID:Corticotropin-releasing hormone signaling in synovial tissue vascular endothelium is mediated through the cAMP/CREB pathway. 1211 66

Chronic stress and probably the accompanying changes in personal behaviours can influence life expectancy. The role of adrenocorticotropic hormone (ACTH) and cortisol in atherosclerosis is not widely accepted and incompletely characterized. Several reports support a role of these hormones in atherogenesis by modulating the function of vascular endothelium, the recruitment of circulating monocytes to the artery wall and their differentiation into macrophages- foam cells, by controlling the expression of pro- and anti-inflammatory interleukins. Previous reports suggested an important role of ACTH and cortisol in the modulation of atherosclerotic plaque progression by removal of excess free cholesterol from macrophages. Studies suggested a crucial role of these hormones on the development of acute coronary syndromes [(ACS); unstable angina, and acute myocardial infarction] and stroke, by modulating platelet aggregation and thrombus formation. This review focuses on the identified mechanisms and roles of ACTH and cortisol in atherogenesis, progression of atherosclerosis and the development of ACS. Finally, it proposes experimental studies to evaluate the therapeutic potential of new glucocorticoid antagonists, the effects that may derive from the inhibition cortisol synthesis and the role of 11beta-hydroxysteroid dehydrogenase type 1 inhibitors in atherogenesis, progression of atherosclerosis and the development of ACS. These hormones may be a possible additional target for the prevention and treatment of atherosclerosis.
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PMID:The role of the stress-related anti-inflammatory hormones ACTH and cortisol in atherosclerosis. 1948 4

1. Obesity is a metabolic disease of pandemic proportions largely arising from positive energy balance, a consequence of sedentary lifestyle, conditioned by environmental and genetic factors. Several central and peripheral neurohumoral factors (the major ones being the anorectic adipokines leptin and adiponecin and the orexigenic gut hormone ghrelin) acting on the anorectic (pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript) and orexigenic (neuropeptide Y and agouti gene-related protein) neurons regulate energy balance. These neurons, mainly in the arcuate nucleus of the hypothalamus, project to parts of the brain modulating functions such as wakefulness, autonomic function and learning. A tilt in the anorectic-orexigenic balance, perhaps determined genetically, leads to obesity. 2. Excess fat deposition requires space, created by adipocyte (hypertrophy and hyperplasia) and extracellular matrix (ECM) remodelling. This process is regulated by several factors, including several adipocyte-derived Matrix metalloproteinases and the adipokine cathepsin, which degrades fibronectin, a key ECM protein. Excess fat, also deposited in visceral organs, generates chronic low-grade inflammation that eventually triggers insulin resistance and the associated comorbidities of metabolic syndrome (hypertension, atherosclerosis, dyslipidaemia and diabetes mellitus). 3. The perivascular adipose tissue (PVAT) has conventionally been considered non-physiological structural tissue, but has recently been shown to serve a paracrine function, including the release of adipose-derived relaxant and contractile factors, akin to the role of the vascular endothelium. Thus, PVAT regulates vascular function in vivo and in vitro, contributing to the cardiovascular pathophysiology of the metabolic syndrome. Defining the mechanism of PVAT regulation of vascular reactivity requires more and better controlled investigations than currently seen in the literature.
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PMID:Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint. 2108 97


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