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)

We have previously demonstrated low levels of immunoreactive (ir)-beta-endorphin (beta-EP) and ir-ACTH in a subpopulation of mouse spleen macrophages, which is consistent with an involvement of opioid peptides in modulation of immune responses. Gel chromatography studies suggested the presence of an approximately 3.5,000-molecular weight (mol wt) species, putatively beta-EP, an approximately 11.5,000-mol-wt species, putatively beta-lipotropin, and a higher molecular weight species (putative beta-EP precursor, pro-opiomelanocortin (POMC). In this study we have extended our original findings by demonstrating the presence of messenger RNA for POMC by the use of a complementary DNA probe and Northern blot analysis of extracts of mouse and rat spleen. In addition, using high performance liquid chromatography (HPLC), we have shown that the major endorphin species in mouse spleen macrophages is beta-EP1-31, and that there are smaller amounts of each of the acetylated forms, N-acetyl-beta-EP1-16 (alpha-endorphin), N-acetyl-beta-EP1-17 (gamma-endorphin), N-acetyl-beta-EP1-27, and N-acetyl-beta-EP1-31. We interpret these studies as showing that (a) the spleen is an organ of POMC synthesis and that (b) the predominant COOH-terminal product of macrophage POMC is the opiate-receptor active species beta-EP1-31.
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PMID:Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. 242 57

A 64 year old woman with a pancreatic islet cell tumor developed Cushing's syndrome. Glucocorticoid secretion did not decrease after low or high dose dexamethasone administration, and the Cushing's syndrome was cured by removal of tumor tissue. Immunohistochemistry and radioimmunoassays revealed the presence of immunoreactive ACTH, beta-endorphin and alpha-MSH in the tumor cells. Gel-permeation chromatography confirmed that beta-endorphin was the predominant opioid peptide produced by the tumor. The tumor was shown to contain a single 1.2 kilobase RNA species which hybridized to a 32P human POMC-cDNA; this POMC RNA was identical in size to that isolated from a normal human pituitary. In dispersed monolayer culture, CRF failed to elicit ACTH release from the tumor cells, but dexamethasone caused a paradoxical increase in ACTH secretion in vitro. This study demonstrates that aberrant regulation of POMC synthesis and peptide processing can be seen in tumors which synthesize a POMC RNA identical in size to that made in the pituitary gland.
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PMID:Aberrant production and regulation of proopiomelanocortin-derived peptides in ectopic Cushing's syndrome. 245 59

1. Immunoreactive (IR)-met-enkephalin and beta-endorphin contents in the hypothalamus and the pituitary were measured in alloxan-diabetic rats with or without insulin treatment. 2. Both IR-met-enkephalin and IR-beta-endorphin in the pituitary were substantially reduced in alloxan-diabetic rats 1 month after treatment. 3. Hypothalamic IR-beta-endorphin content was also significantly lower. 4. Gel-filtration chromatography showed that the peaks co-eluting with met-enkephalin precursor, met-enkephalin and beta-endorphin were lower in the pituitaries from the diabetic rats, whereas the peaks co-eluting with beta-endorphin precursor and beta-lipotropin were not. 5. In another experiment, the IR-beta-endorphin contents of the neuro-intermediate lobe and hypothalamus, but not the anterior lobe were significantly lowered in diabetic rats, whereas IR-met-enkephalin contents were significantly reduced in both the anterior and neuro-intermediate lobe. 6. All these changes were reversed by insulin treatment. 7. As a decrease in general protein synthesis could not explain the recorded changes, these results suggest a possible direct role of insulin in regulating the opioid peptide content of the hypothalamus and pituitary.
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PMID:Changes in met-enkephalin and beta-endorphin contents in the hypothalamus and the pituitary in diabetic rats: effects of insulin therapy. 252 66

beta-Endorphin and ACTH derive from a common peptide precursor. Although much is known about the physiological patterns of ACTH release, neither the minute to minute regulation of beta-endorphin secretion nor its temporal relationship to cortisol has been characterized. As an initial step to defining the regulation of beta-endorphin release in man, we studied the circadian periodicity, ultradian rhythmicity, and episodic pulsatility of serum beta-endorphin concentrations in seven normal men. Blood sampling was conducted at 10-min intervals for 24 h, and the subsequent serum samples were assayed by a two-site immunoradiometric assay. Computerized analysis of the subsequent beta-endorphin time series revealed a mean beta-endorphin pulse frequency of 13 +/- 1 (+/- SE) peaks/24 h, corresponding to an interpulse interval of 100 +/- 7 min. The mean maximal peak height of beta-endorphin pulses was 31 +/- 3 pg/mL (9.0 +/- 0.8 pmol/L), which represented an incremental increase of 11 +/- 1 pg/mL 3.2 +/- 0.4 pmol/L; 63 +/- 13%) above the preceding nadir. The average beta-endorphin peak exhibited a duration of 68 +/- 6 min. Fourier analysis revealed a significant circadian amplitude of 6 +/- 1 pg/mL (1.6 +/- 0.4 pmol/L; 23% of the 24-h mean concentration), with an acrophase (time of maximum value) at 1043 h (+/- 40 min). Spectral analysis also disclosed beta-endorphin rhythms with mean periodicities of 29 +/- 4, 42 +/- 4, and 61 +/- 5 min. Gel filtration chromatography confirmed that serum beta-endorphin peaks contained significantly more immunoactive beta-endorphin [62 pg/mL (18 pmol/L)] than did the flanking nadirs [16 and 18 pg/mL (4.6 and 5.2 pmol/L)]. Auto- and cross-correlation analyses of serum beta-endorphin and cortisol concentrations followed by autoregressive modeling disclosed that all seven men had significant positive cross-correlations between serum beta-endorphin and cortisol considered simultaneously or when cortisol lagged beta-endorphin by 10 min. A negative cross-correlation was found in five of the seven men when cortisol was considered to lead beta-endorphin by 20 or 30 minutes. We conclude that beta-endorphin is released physiologically in a pulsatile manner with circadian and ultradian rhythmicity and a close temporal coupling to cortisol.
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PMID:Circadian, ultradian, and episodic release of beta-endorphin in men, and its temporal coupling with cortisol. 252

Gel-permeation high-performance liquid chromatography (GP-HPLC) columns provide rapid high-resolution separations but are frequently limited to analytical tasks because the injection volumes must be small. The reduction of volume required for the loading of solutes can often be impractical and lead to poor recoveries. We have developed a trace-enrichment technique to circumvent this problem. By placing a Waters Guard Pak within the loop of a Valco injector and connecting a pump to the injection port it is possible to concentrate proteins and peptides onto the guard column from relatively large volumes. Enrichment onto a reversed-phase guard column insert is achieved by loading solutes in an aqueous solution or one of low organic solvent concentration. Provided that the GP-HPLC is mean-while equilibrated with a solvent system of sufficiently high organic solvent concentration (i.e., 40% acetonitrile containing 0.1% trifluoroacetic acid) it is possible to elute material that has been loaded in this manner by simply placing the injection loop in line with the column. The solvent strength abruptly increases and the peptide or protein sample is loaded onto the column in a very small volume. We have applied this loading principle to both analytical and semipreparative problems. The amino-terminal fragment of pro-opiomelanocortin (POMC) has been extracted from a single human fetal pituitary (18 weeks gestation) and characterized in terms of its molecular weight. This study indicated that no proteolytic processing of the amino-terminal fragment of POMC takes place at this stage in development. In a larger scale application the amino-terminal fragment of POMC was purified from bovine anterior pituitaries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A trace-enrichment technique for the loading of gel-permeation high-performance liquid chromatography columns. 267 75

Neonatal rats show a period of diminished adrenocorticotropin responsiveness to stress during the first 2 weeks of life. To test whether beta-endorphin-like peptides (beta-EPLPs) follow the same pattern of hyporesponsiveness to stress during this period, we examined the ontogeny of the beta-EPLPs response to two different types of stressors (ether vapors and cold) during the early postnatal period. The content of beta-EPLPs was estimated in the serum, the pituitary gland and the hypothalamus prior to and 5 min following exposure to stressful stimuli. Furthermore, to determine the relationship between the responsiveness of beta-EPLPs to stress and that of the hypothalamic-pituitary-adrenal axis in the developing rat, the content of hypothalamic corticotropin-releasing factor (CRF) and serum corticosterone was estimated prior to and following stress. Results indicated that stress induced an increase in the serum corticosterone levels at all ages tested (days 1-22), however, the stress-induced elevations of serum corticosterone were significantly greater on days 1 and 22 than on days 3-14. Significant stress-induced elevations of serum immunoreactive beta-endorphin (ir-beta-EP) were observed on days 14 and 22 of life, while changes on days 1, 3, 8 and 10 were either nonexistent or not statistically significant. Gel filtration analysis revealed that the increases in serum ir-beta-EP following stress on days 14 and 22 resulted primarily from increases in the beta-lipotropin component with lesser increases in the beta-endorphin component. Pituitary content of beta-EPLPs was not affected by stress before day 10, but was markedly reduced in the 10- and 14-day-old rats, following stress. A similar, although not statistically significant decrease was observed in the pituitary content of beta-EPLPs of the 22-day-old rats after exposure to stress. Furthermore, exposure to cold stress in the 14-day-old rats induced more pronounced changes in the serum ir-beta-EP and corticosterone levels as well as in the pituitary ir-beta-EP content than it did with ether stress. Despite variations in serum corticosterone as well as serum and pituitary content of beta-EPLPs, no changes in the hypothalamic ir-beta-EP content were seen in rats after subjection to stress, while small, not statistically significant reductions in the hypothalamic CRF content were observed at 5 min after the onset of stress in the 14-and 22-day-old rats. Thus, during the first 2 weeks of life neonatal rats exhibit a reduced capacity to secrete beta-EPLPs in response to stress.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ontogeny of the beta-endorphin response to stress in the rat: role of the pituitary and the hypothalamus. 281 72

Corticotropin-releasing factor (CRF)-like activity in bovine adrenal medulla extracts were characterized by measurement of adrenocorticotropin (ACTH) release from rat anterior pituitary cells in vitro, and by a sensitive heterologous radioimmunoassay (RIA) for bovine hypothalamic CRF. Bovine adrenal medulla was boiled in 2 M acetic acid, homogenized, and submitted to acetone precipitation, followed by batch-wise treatment with C-18 resin. The partially purified adrenal medulla extract showed significant stimulation of ACTH release in vitro and CRF-like immunoreactivity (CRF-IR). After subsequent ion exchange chromatography on a SP-Sephadex column, most CRF bioactivity (CRF-BA) and CRF-IR were eluted with weakly basic materials in the SP-II fraction in which synthetic CRF is eluted. Minor CRF-BA and CRF-IR were also eluted in the SP-III fraction which contained basic peptides. Upon Sephadex G-50 gel filtration of the SP-II fraction, CRF-BA and CRF-IR coeluted, but slightly later than synthetic bovine CRF. However, rechromatography of the major CRF activity on a Sephadex G-50 column and reverse phase and ion exchange high performance liquid chromatographies (HPLC) indicated that CRF-BA and CRF-IR were eluted in the identical fraction as synthetic bovine CRF. Gel filtration in the SP-III fraction on a Sephadex G-50 column showed a few low CRF-BA peaks which lacked CRF-IR. This CRF-BA, however, contributed to less than 5% of the total CRF-BA. These results indicate that the majority of CRF-BA and CRF-IR in the bovine adrenal medulla is chromatographically indistinguishable from bovine hypothalamic CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biological and immunological characterization of corticotropin-releasing activity in the bovine adrenal medulla. 283 3

Immunoreactive (IR) POMC peptides have been found in several rat nonpituitary tissues. We found IR-ACTH, IR-beta-endorphin (beta END), and IR-gamma MSH in extracts from the following eight rat nonpituitary tissues, listed in order of decreasing POMC peptide concentrations: testis, duodenum, kidney, colon, liver, lung, stomach, and spleen, but not in adrenal or muscle extracts. Concentrations were very low and ranged from less than 0.00003% to 0.0005% of pituitary levels. In testis, duodenum, and colon, IR-gamma MSH and IR-beta END concentrations were only 5-37% of IR-ACTH levels. Gel filtration chromatography showed that IR-ACTH and IR-beta END coeluted in a major peak of 15,000 daltons, which is slightly larger than expected for a C-terminal peptide containing rat ACTH and beta-lipotropin. There were also a minor higher mol wt peak of IR-ACTH and IR-beta END and a minor IR-beta END peak that eluted in the position of mature beta END. There was no peak of IR-ACTH that corresponded to the size of mature ACTH. To determine whether these nonpituitary tissues also contained a POMC-like mRNA, which would confirm that the peptides were synthesized locally within the tissues, we examined poly(A) RNA prepared from 10 nonpituitary tissues and total RNA from pituitary by Northern blot hybridization for the presence of a POMC-like mRNA with an exon 3 riboprobe. Pituitary contained a single POMC mRNA species of about 1000 nucleotides. A short POMC-like mRNA of about 800 bases was found in all nonpituitary tissues, except spleen and muscle. Compared to POMC mRNA levels in pituitary, the concentration of POMC-like mRNA was 0.5% in testis and 0.03-0.07% in the other tissues. The ratio of POMC-like mRNA to IR-POMC peptide concentrations in nonpituitary tissues was at least 1000 times greater than that in the pituitary. We conclude that the POMC gene is expressed in many nonpituitary tissues and that either the short POMC-like mRNA is translated much less efficiently or POMC peptides are released or degraded much more rapidly in nonpituitary tissues than in the pituitary.
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PMID:Immunoreactive proopiomelanocortin (POMC) peptides and POMC-like messenger ribonucleic acid are present in many rat nonpituitary tissues. 283 69

N alpha-Acetyltransferase, which catalyzes the transfer of an acetyl group from acetyl coenzyme A to the alpha-NH2 group of proteins and peptides, was isolated from Saccharomyces cerevisiae and demonstrated by protein sequence analysis to be NH2-terminally blocked. The enzyme was purified 4,600-fold to apparent homogeneity by successive purification steps using DEAE-Sepharose, hydroxylapatite, DE52 cellulose, and Affi-Gel blue. The Mr of the native enzyme was estimated to be 180,000 +/- 10,000 by gel filtration chromatography, and the Mr of each subunit was estimated to be 95,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 9.0, and its pI is 4.3 as determined by chromatofocusing on Mono-P. The enzyme catalyzed the transfer of an acetyl group to various synthetic peptides, including human adrenocorticotropic hormone (ACTH) (1-24) and its [Phe2] analogue, yeast alcohol dehydrogenase I (1-24), yeast alcohol dehydrogenase II (1-24), and human superoxide dismutase (1-24). These peptides contain either Ser or Ala as NH2-terminal residues which together with Met are the most commonly acetylated NH2-terminal residues (Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527). Yeast enolase, containing a free NH2-terminal Ala residue, is known not to be N alpha-acetylated in vivo (Chin, C. C. Q., Brewer, J. M., and Wold, F. (1981) J. Biol. Chem. 256, 1377-1384), and enolase (1-24), a synthetic peptide mimicking the protein's NH2 terminus, was not acetylated in vitro by yeast acetyltransferase. The enzyme did not catalyze the N alpha-acetylation of other synthetic peptides including ACTH(11-24), ACTH(7-38), ACTH(18-39), human beta-endorphin, yeast superoxide dismutase (1-24). Each of these peptides has an NH2-terminal residue which is rarely acetylated in proteins (Lys, Phe, Arg, Tyr, Val, respectively). Among a series of divalent cations, Cu2+ and Zn2+ were demonstrated to be the most potent inhibitors. The enzyme was inactivated by chemical modification with diethyl pyrocarbonate and N-bromosuccinimide.
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PMID:Purification and characterization of an N alpha-acetyltransferase from Saccharomyces cerevisiae. 284 92

In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and beta-endorphin immunoreactivity 2.5-fold (P less than 0.01). Gel filtration of plasma revealed two peaks of beta-endorphin immunoreactivity corresponding to beta-endorphin and beta-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating beta-endorphin immunoreactivity in control animals corresponded to beta-endorphin. Central infusion of the H1-receptor agonist 2-thiazolylethylamine and of the H2-receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and beta-endorphin immunoreactivity concentrations 2- and 3-fold, respectively (P less than 0.01). Infused intracerebroventricularly, the H2-receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and beta-endorphin immunoreactivity (P less than 0.01), whereas the H1-receptor antagonist mepyramine inhibited the peptide responses by 70% (P less than 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine-induced increase in plasma ACTH by 80% (P less than 0.01) and plasma beta-endorphin immunoreactivity by 45% (P less than 0.05), whereas mepyramine or the other H1-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P less than 0.05), but had no effect on the beta-endorphin immunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, beta-lipotropin and beta-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of beta-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H2-receptors, whereas H1-receptors appear to play a minor role.
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PMID:Effect of histamine on the secretion of pro-opiomelanocortin derived peptides in rats. 284 93


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