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)

Acute glucoprivation profoundly stimulated hypothalamic-pituitary-adrenocortical (HPA) and adrenomedullary outflows. Whether these responses reflect a single central mechanism regulated by corticotropin-releasing hormone (CRH) has been unclear. This study examined the role of endogenous CRH in HPA and adrenomedullary responses to hypoglycemia in Sprague-Dawley rats, by using anti-CRH immune serum or a CRH antagonist (alpha-helical h/r CRH9-41, and in Lewis rats, a strain characterized by deficient hypothalamic CRH responses during stress. In conscious Sprague-Dawley rats with indwelling arterial and venous cannulas, insulin (0.3 U/kg was injected iv, and responses of serum glucose concentrations and plasma levels of corticotropin (ACTH) and catechols (including epinephrine, EPI; norepinephrine, NE; dihydroxyphenylalanine, DOPA; dihydroxyphenylglycol, DHPG; and dihydroxyphenylacetic acid, DOPAC) were assessed, with or without pretreatment with anti-CRH immune serum (0.5 or 1.0 ml iv or 10 microl icv) or alpha-helical h/r CRH9-41 (130 nmol iv or 13 nmol icv). Responses to insulin (1.0 U/kg iv) were also measured in conscious juvenile Lewis and Fischer 344/N rats. Insulin-induced hypoglycemia markedly increased plasma levels of EPI and ACTH in all groups. Pretreatment iv with 1/0 ml of anti-CRH immune serum blocked the ACTH response to insulin but failed to attenuate the EPI response. alpha-helical h/r CRH9-41, whether given iv or icv, failed to alter ACTH or EPI responses to insulin, although the antagonist did block EPI responses to icv CRH. Hypoglycemia elicited similar increments in ACTH levels in Lewis rats and Fischer 344/N control rats; and although Lewis rats had lower baseline EPI and smaller responses of NE, DHPG, DOPA, and DOPAC levels, the groups did not differ in proportionate increments in EPI levels. The results indicate that the ACTH response to hypoglycemia depends on availability of CRH outside the blood-brain barrier--presumably in the pituitary gland. The findings with icv alpha-helical h/r CRH9-41 can be explained by failure of the antagonist to reach effective concentrations at central sites of action of endogenous CRH, or by mechanisms other than CRH release determining the adrenomedullary response to hypoglycemia. Lewis rats seem to have less adrenomedullary secretion at baseline and smaller responses of NE synthesis and release during hypoglycemia than do Fischer 344/N rats. Neurochemical evidence for differential adrenomedullary and sympathoneural responses during hypoglycemia in all three rat strains is inconsistent with Cannon's view of a functionally unitary sympathoadrenal system. Lewis rats have deficient CRH responses to some stressors but not to others, or else pituitary-adrenomedullary responses in this setting depend on mechanisms other than CRH release in the brain. Both explanations are inconsistent with the doctrine of non-specificity, the main tenet of Selye's stress theory.
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PMID:Role of CRH in glucopenia-induced adrenomedullary activation in rats. 868 Apr 14

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.
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PMID:The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice. 906 2

The effect of immunoneutralization of beta-endorphin on the suckling-induced prolactin increase and on the activity of the tuberoinfundibular dopaminergic (TIDA) neurons was determined in lactating female rats between days 8 - 12 post-partum. Two antisera were used in the immunoneutralization studies. Both were specific for beta-endorphin, exhibiting little cross reactivity with met- or leu-enkephalin or dynorphin. Antisera to beta-endorphin completely abolished the suckling-induced prolactin increase indicating that this endogenous opioid peptide is involved in this response. Suckling significantly inhibited DOPA accumulation in the median eminence and antiserum to beta-endorphin did not prevent this inhibition. Additionally, 5-endorphin antiserum significantly reduced TIDA neural activity even in pup-deprived dams. These results indicate that beta-endorphin is involved in the prolactin secretory response to suckling but that inhibition of TIDA neuronal activity is not its mechanism of action. Other possible mechanisms are discussed.
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PMID:Immunoneutralization of beta-endorphin blocks prolactin release during suckling without affecting tuberoinfundibular dopaminergic neural activity. 932 72

Free radical melanin centers have been detected in the cell concentrate of bronchoalveolar lavage (BAL) of liquidator of Chernobyl NPP accident. To identify the nature of these centers the EPR technique and the fluorescent technique were used to study BAL of liquidators with lung chronic pathology, their blood, blood components as well as model melanin- and lipofuscin-containing systems: synthetic DOPA-melanin, human melanosome, human lipofuscin, human melanolipofuscin. I Besides that we have investigated the samples of fungi, extracted from lung phlegm of liquidators (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Penicillium Sp., Candida albicans) as well as the melanin, extracted from fungal conidium. It has been shown that the melanin centers found in BAL cells of liquidators is the melanin of melanin-synthesizing mutant fungi Aspergillus fumigatus and Aspergillus flavus. The prolonged gamma-irradiation at low dose rate and the effects of inhaled radioactive particles cause the adaptive mutation of micromycetes producing the chemo- and radioresistant population. We think that the radioactive dust and pathogenic mutant micromycetes were inhaled in lungs of liquidators during their work at the Chernobyl NPP. Thus, one of valid consequences of Chernobyl accident may be the wide fungous of human organs, in particularly, by Aspergillus mutant. The radiation-induced weakening of immune reactions of liquidators promotes the resistance of this fungus mutant infection.
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PMID:[Fungal infection of human organs by resistant melanin-synthesizing species is one of the pathogenic factors and one of the real consequences of the accident at Chernobyl power plant]. 959 25

Previous studies have shown that the endogenous opioid peptides, acting at specific opiate receptor subtypes, are involved in the suckling-induced prolactin secretory response. The prolactin increase elicited by suckling is due, at least in part, to an inhibition of tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus. We investigated the effects of immunoneutralization of dynorphin, leu-enkephalin and met-enkephalin on the suckling-induced prolactin increase and on the activity of the TIDA neurons in lactating female rats between days 7 and 12 postpartum. Rats were injected into the right lateral ventricle with antiserum specific for one of these three peptides. Control rats were administered equal amounts of immunoglobulin proteins. Suckling produced a profound and significant increase in prolactin levels, as well as a decrease in DOPA accumulation in the median eminence of lactating rats. Administration of immunoglobulin concentrations of up to 3.6 microg did not inhibit the prolactin secretory response to the suckling stimulus and did not prevent the suckling-induced inhibition of TIDA neurons. Antisera to all three endogenous opioid peptides abolished the suckling-induced prolactin increase and prevented the inhibition in DOPA accumulation in the median eminence. Thus, the endogenous opioid peptides, dynorphin, leu-enkephalin and met-enkephalin, are essential for the prolactin secretory response to suckling and inhibition of TIDA neuronal activity is at least one of the mechanisms of action utilized by these peptides.
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PMID:Immunoneutralization of endogenous opioid peptides prevents the suckling-induced prolactin increase and the inhibition of tuberoinfundibular dopaminergic neurons. 1077 47

To elucidate the role of dopamine as a neuromediator in the adrenocorticotropic hormone (ACTH) secretion, investigations were carried out with dopaminergic pharmacology drugs on male white Wistar rats. In the first series of experiments, the effects of 200 mg/kg body wt L-DOPA, of the combination of 200 mg/kg L-DOPA and 50 mg/kg body wt carbidopa, and of 2.5 mg/kg body wt bromocriptine, after a single intraperitoneal injection of ACTH in the serum of rats after 30, 90 and 120 min, following the injection, were studied. In the second series of experiments, the effect of 200 mg/kg body wt L-DOPA, of the combination of 200 mg/kg body wt L-DOPA and 50 mg/kg body wt carbidopa, of 1 mg/kg body wt bromocriptine, after intraperitoneal injection, on the concentration of ACTH in the serum within 7 days, were assessed. The inhibition of agonists of dopamine after ACTH secretion with repeated application has been shown. Using a radioimmunology assay with test kits, the amount of ACTH in the serum was determined.
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PMID:Influence of dopamine energic pharmacology drugs on secretion of the adrenocorticotropic hormone from the hypophysis. 1095 29

The effect of neonatal treatment with monosodium L-glutamate (MSG) on the dopaminergic systems of the medial basal hypothalamus has been investigated using tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) immunocytochemistry. Changes in plasma levels of prolactin (PRL) and alpha-melanocyte-stimulating hormone (MSH) have also been determined in intact and in MSG-treated rats after inhibition of TH by alpha-methyl-p-tyrosine (alpha-MpT) or without inhibition of enzyme activity. Monosodium glutamate resulted in a 40% reduction in the number of TH immunopositive tuberoinfundibular neurons, but no change in the number of AADC-positive tuberoinfundibular nerve cells, indicating that this reduction has occurred mainly in TH-positive but AADC-negative elements, i.e., in L-DOPA-ergic neurons. In contrast, MSG did not cause changes in the number of TH and AADC immunoreactive neurons of the periventriculohypophysial and tuberohypophysial dopaminergic systems, and it did not influence basal plasma PRL levels. alpha-methyl-p-tyrosine has increased plasma PRL concentrations in both control and MSG-treated rats of both sexes, but significantly higher responses were detected in females. None of the treatments had any effect on plasma MSH level. These findings suggest that MSG affects primarily L-DOPA-ergic neurons located in the ventrolateral part of the arcuate nucleus, but not dopaminergic neurons situated in the dorsomedial part of the arcuate nucleus; neither PRL nor MSH secretion is altered by MSG; a significant sex difference exists in the pituitary PRL response to inhibition of TH, and this response is not affected by MSG.
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PMID:Effect of neonatal treatment with monosodium glutamate on dopaminergic and L-DOPA-ergic neurons of the medial basal hypothalamus and on prolactin and MSH secretion of rats. 1159 61

Many melanocyte or skin equivalent models have been used to evaluate the potential efficacy of melanogenic compounds to regulate pigmentation, but there has been great variation in results, partially stemming from the use of different cell lines and diverse conditions for the melanogenic assays. In an earlier report, we optimized a microtiter format assay system to screen potential bioactive compounds using immortalized melan-a melanocytes. That assay system, termed the STOPR protocol, allowed effects on melanocyte proliferation and differentiation to be assessed in a highly sensitive, reproducible, and cost-effective manner. However, in the skin and hair, melanocytes interact with keratinocytes, fibroblasts, and other cell types, and testing of putative bioactive compounds on melanocytes alone in culture does not allow one to observe the interactions with those other cell types, such as would occur in vivo. Therefore, we developed a melanocyte-keratinocyte coculture protocol that allows testing of compounds for potential effects on pigmentation in a more physiologically relevant context. It is a sensitive, reproducible, and reliable model for testing melanogenic regulators, and we have standardized it with known melanogenic inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and stimulators (alpha-melanocyte-stimulating hormone, 8-methoxypsoralen, and 3,4-dihydroxyphenylalanine). This coculture system allows for large-scale screening of candidate compounds in conjunction with the STOPR protocol and provides a more physiologically relevant system to study melanocyte-keratinocyte interactions and to elucidate the regulatory mechanisms of melanogenic compounds.
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PMID:A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. 1205 55

Ultraviolet B radiation increases DOPA-positive melanocytes in the skin specifically at the site of exposure. We found unexpectedly that ultraviolet B irradiation of the eye increased the concentration of alpha-melanocyte-stimulating hormone in plasma and systemically stimulated epidermal melanocytes in mice. To test the possible involvement of hypothalamopituitary proopiomelanocortin system in the systemic activation of skin melanocytes, ultraviolet B was also irradiated to the eye after hypophysectomy. Hypophysectomy strongly inhibited the ultraviolet B-induced stimulation of melanocytes. To elucidate the pathway by which ultraviolet B irradiation of the eye activated the hypothalamopituitary system, we examined the effect of bilateral ciliary ganglionectomy and denervation of the optic nerves on the ultraviolet B-induced melanocyte stimulation. Ciliary ganglionectomy, but not optic nerve denervation, strongly inhibited melanocyte stimulation by localized irradiation of the eye. Furthermore, melanocyte stimulation by localized ultraviolet B irradiation of the eye was not observed in mice that lack the inducible type of nitric oxide synthase. These results clearly indicate that a signal evoked by ultraviolet B irradiation of the eye is transmitted in a nitric oxide-dependent manner through the ciliary ganglia involving the first branch of the trigeminal nerve to the hypothalamopituitary proopiomelanocortin system, resulting in upregulation of alpha-melanocyte-stimulating hormone secretion and consequent stimulation of melanocytes in the skin. The novel network involving the trigeminal nerve and nitric oxide-dependent signaling pathway might play important parts in the activation of proopiomelanocortin-dependent biologic reactions, such as alpha-melanocyte-stimulating hormone-induced stimulation of melanocytes in the skin, in ultraviolet B-enriched environments.
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PMID:Ultraviolet B irradiation of the eye activates a nitric oxide-dependent hypothalamopituitary proopiomelanocortin pathway and modulates functions of alpha-melanocyte-stimulating hormone-responsive cells. 1253 8

Reconstituted 3-dimensional human skin equivalents containing melanocytes and keratinocytes on an artificial dermal substitute are gaining popularity for studies of skin metabolism because they exhibit morphological and growth characteristics similar to human epidermis. In this study, we show that such a pigmented epidermis model can be used to assess the regulation of pigmentation by known melanogenic compounds. In monolayers or in melanocyte-keratinocyte co-cultures, melanocyte-keratinocyte interactions are missing or are spatially limited. The commercial skin equivalents used in this study were derived from epidermal cells obtained from donors of three different ethnic origins (African- American, Asian, and Caucasian), and they reflect those distinct skin phenotypes. We used these pigmented human epidermis models to test compounds for potential effects on pigmentation in a more physiologically relevant context, which allows further characterization and validation of interesting melanogenic factors. We used known melanogenic stimulators (alpha-melanocyte-stimulating hormone and 3,4-dihydroxyphenylalanine) and inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and examined their effects on the production of melanin and its distribution in upper layers of the skin. Our studies indicate that commercial skin equivalents provide a convenient and cost-effective alternative to animal testing for evaluating the regulation of mammalian pigmentation by melanogenic factors and for elucidating their mechanisms of action.
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PMID:Reconstituted 3-dimensional human skin of various ethnic origins as an in vitro model for studies of pigmentation. 1281 30


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