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)

Anterior pituitary corticotropes increase in number after stimulation by adrenalectomy or corticotropin-releasing hormone (CRH). However, is this brought about by mitoses? Furthermore, as epidermal growth factor (EGF) is a potent secretagogue for corticotropes, is it also a mitogen? To address these questions, populations of corticotropes enriched to 88-97% by counterflow centrifugation were studied after growth in 0-10 nM CRH with and without 0.1-10 ng/ml EGF. Three types of assays were used to detect changes in mitotic cells or cell number. An enzyme immunoassay for bromodeoxyuridine uptake during DNA synthesis [bromodeoxyuridine (BrDU) uptake] detected a 3-fold increase in optical density readings in the presence of 0.5 nM CRH or EGF. Together the peptides increased the optical density to 4.8-fold basal levels. No further increases in BrDU uptake were seen with higher concentrations of CRH or EGF. Cytochemical detection of BrDU uptake by immunolabeled corticotropes showed BrDU in 18 +/- 2% of 3- to 5-day ACTH cells. In the presence of 0.5 nM CRH or 0.5 ng/ml EGF, this value increased to 37 +/- 3% or 34 +/- 2% of ACTH cells, respectively. Together CRH and EGF stimulated increases in mitotic activity so that 47 +/- 4% of the ACTH cells were labeled for BrDU after a 1-h exposure. Cell growth/cell death assays in 3-(4,5-dimethyltiazol-2-yl)2,5- diphenyl tetrazolium bromide were also used to detect changes in overall cell number or cell survival in the same groups of enriched corticotrope cultures. Both 0.5 nM CRH and 0.5 ng/ml EGF caused increases to 1.5- to 1.7-fold basal readings. However, higher concentrations did not stimulate increases in number, and their combined effects were not additive. These studies show that CRH and EGF can be mitogens for ACTH-bearing corticotropes, in a limited dose range. In a higher dose range, their differentiating effects may eliminate dividing cells and retard further growth of the population.
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PMID:Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. 789 69

The present study examined the effects of gamma-aminobutyric acid (GABA) agonists and antagonists on basal periventricular-hypophysial dopaminergic (PHDA) neuronal activity with a focus on the role of endogenous GABA in mediating 5-hydroxytryptamine- and stress-induced decreases in PHDA neuronal activity. PHDA neuronal activity was estimated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in terminals of these neurons in the intermediate lobe of the pituitary. Plasma concentrations of alpha-melanocyte-stimulating hormone (alpha MSH) also were determined to provide a further index of PHDA neuronal activity. Administration of the GABAB agonist baclofen, but not the GABAA agonist isoguvacine, produced dose- and time-related decreases in intermediate lobe DOPAC concentrations and corresponding increases in plasma alpha MSH concentrations. Administration of either the GABAA antagonist SR-95,531 [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide] or GABAB antagonists 2-hydroxysaclofen and CGP-35,348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid; SR-95-531 did not alter basal intermediate lobe DOPAC concentrations or plasma alpha MSH concentrations per se, indicating that endogenous GABA does not tonically inhibit PHDA neuronal activity or alpha MSH secretion. 2-Hydroxysaclofen and CGP-35,348 did, however, reverse the baclofen-induced decrease in intermediate lobe DOPAC concentrations and increase in plasma alpha MSH concentrations. In a similar fashion, 2-hydroxysaclofen blocked the inhibitory effects of stress and the 5-hydroxytryptamine2/1c receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane] on PHDA neuronal activity. These results indicate that GABAB and not GABAA receptor activation inhibits basal PHDA neuronal activity, and that GABAB receptor activation mediates the inhibitory effects of 5-hydroxytryptamine and stress on PHDA neurons.
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PMID:gamma-Aminobutyric acid receptor-mediated regulation of periventricular-hypophysial dopaminergic neurons: possible role in mediating stress- and 5-hydroxytryptamine-induced decreases in neuronal activity. 796 62

The present study was designed to investigate the modulatory effects of blockade of spinal GABAA and GABAB receptors on antinociception induced by supraspinally administered mu- and epsilon-opioid receptor agonists. The effects of intrathecal (i.t.) injections with GABAA and GABAB receptor antagonists, SR 95531 [2-(3-carboxypropyl)-3-amino-6-(4-mehylphenyl)pyridazinium bromide] and 5-aminovaleric acid, respectively, on the antinociception induced by morphine (a mu-opioid receptor agonist) and beta-endorphin (an epsilon-opioid receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. Antinociception was assayed using the tail-flick test. The i.t. injection of SR 95531 (0.04-0.16 nmol) and 5-aminovaleric acid (32.5-130 nmol), administered alone did not affect the latencies of the tail-flick response, but selectively antagonized the inhibition of the tail-flick response induced by muscimol (a GABAA receptor agonist) and baclofen (a GABAB receptor agonist), respectively. The i.t. injection of SR 95531 attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered morphine, without affecting the i.c.v. administered beta-endorphin-induced response. 5-Aminovaleric acid attenuated dose-dependently the inhibition of the tail-flick response induced by beta-endorphin, without affecting the response to i.c.v. administered morphine. Our results indicate that GABAA but not GABAB receptors located at the spinal cord appears to be involved in the antinociception induced by morphine administered supraspinally whereas GABAB but not GABAA receptors located at the spinal cord may be involved in the antinociception induced by supraspinally administered beta-endorphin, supporting further the hypothesis that morphine and beta-endorphin administered supraspinally produce their antinociception via the activation of different descending pain inhibitory systems.
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PMID:Effects of GABA receptor antagonists injected spinally on antinociception induced by opioids administered supraspinally in mice. 883 15

Products formed during cyanogen bromide (CNBr) digestion of alpha-endorphin, beta-endorphin, and horse heart myoglobin are examined using reversed-phase high-performance liquid chromatography and electrospray mass spectrometry. It is demonstrated that unstable intermediate reaction products may be formed, as well as oxidized products when the CNBr reaction is performed in 0.1% TFA in water/acetonitrile (6:4 v/v) and that, under other conditions commonly employed for the CNBr cleavage reaction, unstable intermediate products are also generated. The formation of the expected cleavage products is found to be improved by adjusting the hydrolysis conditions. The structure of the intermediate formed from alpha-endorphin is examined using electrospray mass spectrometry in combination with low-energy collision-induced dissociation and tandem mass spectrometry and is shown to have a cyclic hydrated homoserine iminolactone part. The results obtained in this study explain the formation of partially cleaved proteins in the case of Met-Thr-containing sequences, which likely have a cyclic hydrated homoserine iminolactone part instead of the putative homoserine residue.
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PMID:Characterization of unstable intermediates and oxidized products formed during cyanogen bromide cleavage of peptides and proteins by electrospray mass spectrometry. 884 40

Adult male mice were treated with the reversible acetylcholinesterase inhibitor pyridostigmine bromide and its effect on the expression of beta-endorphin and alpha-melanotropin immunoreactivity in motoneurones was examined in the cervical and lumbar spinal cord. Administration of a single dose of either 0.4 micromoles/kg or 2.0 micromoles/kg body weight caused a significant increase in the incidence of beta-endorphin and alpha-melanotropin-immunoreactive motoneurones at 3h after the injection, in both the cervical and lumbar regions of the spinal cord. The immunoreactivity remained elevated for at least 5 days. There was a significantly higher increase in both beta-endorphin and alpha-melanotropin immunoreactive neurones at 3h after the higher dose compared to the lower dose, in both regions of the spinal cord. Repeated administration of a dose of 0.4 micromoles/kg once a day for three weeks caused increases in immunoreactive motoneurones in both regions. In the cervical region the increases were maintained for at least two weeks after the treatment was discontinued but in the lumbar region the levels had returned to normal by one week. A further dose of the drug administered at two weeks after the treatment period caused a significantly greater increase in the lumbar spinal cord than the same dose in untreated mice, indicating that a sensitization of the motoneurones had occurred. The effect of this drug on peptide expression in motoneurones may be secondary to its action to inhibit acetylcholinesterase at the neuromuscular junction.
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PMID:The effect of pyridostigmine administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones. 986 69

Reaction of the melanotropin hormone analogs [Nle(4),D-Phe(7)]-alpha-MSH and [Nle(4),D-Phe(7)]-alpha-MSH(4-10), which were extended at their N-terminus by a thiol-functionalized spacer arm, with preformed liposomes containing thiol-reactive (phospho)lipid derivatives resulted in the aggregation of the vesicles and in a partial leakage of their inner contents. This aggregation/leakage effect, which was only observed when the peptides were covalently conjugated to the surface of the liposomes, was correlated with the fusion of the vesicles as demonstrated by the observed decrease in resonance energy transfer between probes in a membrane lipid mixing assay. A limited fusion was confirmed by monitoring the mixing of the liposome inner contents (formation of 1-aminonaphthalene-3,6,8-trisulfonic acid/p-xylene bis(pyridinium bromide) complex). The membrane-active properties of the peptides could be correlated with changes in the fluorescence emission spectra of their tryptophan residue, which suggested that after their covalent binding to the outer surface of the liposomes they can partition within the core of the bilayers. A blue shift of 10 nm was observed for [Nle(4),D-Phe(7)]-alpha-MSH which was correlated with an increase in fluorescence anisotropy and with changes in the accessibility of the coupled peptide as assessed by the quenching of fluorescence of its tryptophan residue by iodide (Stern-Volmer plots). These results should be related to the previously described capacity of alpha-MSH, and analogs, to interact with membranes and with the favored conformation of these peptides which, via a beta-turn, segregate their central hydrophobic residues into a domain that could insert into membranes and, as shown here, trigger their destabilization.
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PMID:Membrane-active properties of alpha-MSH analogs: aggregation and fusion of liposomes triggered by surface-conjugated peptides. 1177 71

Neutral tryptophan (*Trp) and tyrosine (TyrO(*)) radicals are repaired by certain flavonoids in buffer, in micelles and in human serum albumin (HSA) with corresponding formation of semioxidized flavonoid radicals. In deaerated buffer, *Trp but not TyrO(*) radicals react with catechin. In micelles, quercetin and rutin repair both *Trp and TyrO(*) radicals. In addition to amino acid reactivity, microenvironmental factors and nature of the flavonoids govern this repair. Electron transfer efficiencies from quercetin to negatively charged *Trp radicals are 100% in the micellar pseudophases of positively charged cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55% in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB micelles, quercetin also reacts with the superoxide radical anion. When bound to domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating oxidized molecules with repair efficiencies falling to 7% for oxidized *Trp, Tyr and alpha-MSH and to less than 2% for urate radical. This limited effectiveness is attributed both to the inaccessibility of bound quercetin and rutin toward radicals of circulating molecules and to the diffusion-controlled recombination of these radicals.
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PMID:Mechanisms of flavonoid repair reactions with amino acid radicals in models of biological systems: a pulse radiolysis study in micelles and human serum albumin. 1220 44

Neutral tryptophan (*Trp) and tyrosine (TyrO(*)) radicals are repaired by certain flavonoids in buffer, in micelles and in human serum albumin (HSA) with corresponding formation of semioxidized flavonoid radicals. In deaerated buffer, *Trp but not TyrO(*) radicals react with catechin. In micelles, quercetin and rutin repair both *Trp and TyrO(*) radicals. In addition to amino acid reactivity, microenvironmental factors and nature of the flavonoids govern this repair. Electron transfer efficiencies from quercetin to negatively charged *Trp radicals are 100% in the micellar pseudophases of positively charged cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55% in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB micelles, quercetin also reacts with the superoxide radical anion. When bound to domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating oxidized molecules with repair efficiencies falling to 7% for oxidized Trp, Tyr and alpha-MSH and to less than 2% for urate radical. This limited effectiveness is attributed both to the inaccessibility of bound quercetin and rutin toward radicals of circulating molecules and to the diffusion-controlled recombination of these radicals.
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PMID:Mechanisms of flavonoid repair reactions with amino acid radicals in models of biological systems: a pulse radiolysis study in micelles and human serum albumin. 1204 90

This study shows the characteristics of hormone-dependent lipolysis in white adipose tissues from corpulent spontaneously hypertensive rats (SHR/NDmc-cp(cp/cp)). The glycerol-releasing activity on addition of norepinephrine (NE) and corticotropin (ACTH) was diminished in slices of epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats compared with those from Wistar Kyoto rats and lean spontaneous hypertensive rats (SHR/NDmc-cp(+/+)). 8-Bromo-cyclic adenosine monophosphate had a slight effect on lipolysis in epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats, and addition of NE and ACTH resulted in a slight accumulation of cyclic adenosine monophosphate in epididymal adipose tissue from cp/cp rats. Therefore, the alteration of hormone-dependent lipolysis-related genes was analyzed using quantitative real-time polymerase chain reaction. It was found that the expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin messenger RNAs was limited in epididymal, retroperitoneal, mesenteric, and subcutaneous adipose tissues from cp/cp rats compared with +/+ rats. These results indicate that in white adipose tissue from cp/cp rats, the diminished lipolytic response to NE and ACTH may be caused by impaired expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin.
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PMID:Characteristics of lipolysis in white adipose tissues of SHR/NDmc-cp rats, a model of metabolic syndrome. 1751 19

The alpha-melanocyte-stimulating hormone (alpha-MSH) has been shown to interact with various cells of the immune and inflammatory systems and down-regulate either the production or the action of proinflammatory cytokines. In this study, we investigated the potential of alpha-MSH to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from peripheral blood mononuclear cells (PBMCs) in rats. Pancreatic islets were cocultured with PBMCs in a transwell system during stimulation by phorbol myristic acid and ionomycin. alpha-MSH (50 nmol/L) was added to PBMCs for 2 hours before coculture. Viability and apoptosis of islets were observed by the 3-(4,5-dimethylthiazole-2-yl)-, 5-diphenyltrazolium bromide assay and flow cytometry. We measured inflammatory cytokines and nitric oxide (NO). Insulin release from islets cocultured with mononuclear cells was checked as the metric of islet function. In comparison to the control group, the viability of islets with alpha-MSH-treated mononuclear cells was increased and apoptosis reduced significantly. Inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1beta, were significantly reduced among the alpha-MSH-treated group. NO production in the alpha-MSH-treated group was decreased significantly. Insulin secretory function of the islets recovered in conditions of alpha-MSH treatment. This study demonstrated that alpha-MSH protected pancreatic islet cells from PBMC-mediated cytotoxicity and preserved insulin secretory function. This treatment may have the potential to improve graft survival in clinical islet transplantation.
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PMID:Protective effect of alpha-melanocyte-stimulating hormone on pancreas islet cell against peripheral blood mononuclear cell-mediated cytotoxicity in vitro. 1758 Jan 98


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