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)

There is strong evidence that the hypophyseal neurointermediate lobe (NIL) mediates 17 beta-estradiol (E2)-induced PRL secretion in rats. Our laboratory has previously demonstrated that E2 stimulates NIL cells to release an activity that acutely increases the relative abundance of PRL-releasing cells in anterior pituitary (AP) cell cultures. We later found that secretory products of the NIL melanotropes, specifically the acetylated forms of alpha MSH and beta-endorphin (beta END), can account for this activity. Given that blood from the NIL initially perfuses the region of the AP proximal to the NIL, we tested the hypothesis that this specific area was preferentially responsive to the lactotrope recruitment activities. AP glands from ovariectomized rats were dissected into an inner zone, proximal to the NIL, and the remaining outer zone of the gland, then dispersed with trypsin. The resulting cells were cultured for 16 h, either alone or in coculture with NIL cells, and subsequently treated with medium alone (control) or with alpha MSH, beta END, or E2 (all at 1 x 10(-7) M) for 3 h and then subjected to reverse hemolytic plaque assays for PRL release. Under control conditions, the proportion of PRL-secreting cells was significantly greater in cultures from the outer zone of the AP than in those from the corresponding inner zone of the gland. Treatment of AP cells from the inner zone with alpha MSH, beta END, or the E2-induced NIL activity significantly increased the percentage of PRL secretors by about 8% of all AP cells. In contrast, the fraction of PRL-secreting cells in cultures from the outer zone was not affected by these treatments. We conclude that the recruitment of PRL-secreting cells in response to products of the NIL occurs only in that region of the AP proximal to the NIL.
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PMID:Neurointermediate lobe peptides recruit prolactin-secreting cells exclusively within the central region of the adenohypophysis. 133 43

Astrocytes were prepared from rats of 4 ages, embryonic day 20, postnatal days 3 and 8, and adult, in order to study the developmental time course of expression of enkephalin and somatostatin (SS). Glial fibrillary acidic protein (GFAP) content was constant in both cortical and cerebellar astrocytes prepared from all ages. SS mRNA and peptide decreased over this developmental time course in cerebellar astrocytes; the time course of changes in SS mRNA paralleled that for rat cerebellum. Proenkephalin (PE) mRNA increased about 3-fold in cerebellar astrocytes from embryonic day 20 to adult but remained constant in cortical astrocytes; in contrast, PE mRNA showed a 10- to 12-fold increase in rat cerebellum and cortex developmentally. For both cerebellar and cortical astrocytes, free met-enkephalin decreased from embryonic day 20 to adult, whereas total met-enkephalin (measured following trypsin-carboxypeptidase B digestion of the extracts) increased. These results suggest (1) that there is a developmental regulation of the expression of both enkephalin and SS peptides in astrocytes, and (2) that the regulation occurs at the level of transcription for SS but at the level of precursor processing for PE. Possible trophic functions for astrocyte-derived peptides early in CNS development are discussed.
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PMID:Developmental expression of the proenkephalin and prosomatostatin genes in cultured cortical and cerebellar astrocytes. 135 15

A vaccinia virus (VV) vector was used to express rat plasma kallikrein (rPK) in the constitutively secreting cells, BSC-40, and in the endocrine regulated cells, AtT-20. Using a specific rPK antibody and a fluorogenic substrate, Phe-Phe-Arg-AMC, we demonstrated that in both cell lines VV infections resulted in the synthesis of an immunoreactive enzyme predominantly present as a zymogen which can be activated with trypsin. Stimulation of VV:rPK-infected AtT-20 cells with either 5mM 8-bromo-cAMP or 56 mM KCl resulted in a different pattern of rPK and ACTH secretion, strongly suggesting that rPK follows the constitutive secretory pathway. Finally, the 10% rPK activity found within AtT-20 cell extracts had no effect on pro-opiomelanocortin (POMC) processing either intracellularly or extracellularly. The above data show that the biosynthetic machinery of both cell lines analyzed does not allow the efficient activation of plasma prekallikrein. Finally, despite the PK's demonstrated ability to cleave various hormone precursors in vitro at pairs of basic residues, in vivo, we did not obtain evidence that this hepatic enzyme can also act as an intracellular pro-protein processing enzyme.
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PMID:Expression and sorting of rat plasma kallikrein in POMC-producing AtT-20 cells. 185 25

Many neuroendocrine precursor proteins, such as proopiomelanocortin (POMC), are cleaved in a tissue specific manner at distinct pairs of basic amino acids. Elucidating the specificity of the prohormone endoprotease(s) is essential to understanding cleavage specificity. However, isolation of these enzymes has been difficult, due to the inability to distinguish authentic maturation enzyme from the many other trypsin-like activities present in tissue homogenates. Recently, a "signature" of the insulin cell endoprotease(s) was defined in vivo by assessing the processing of a series of mutant cleavage sites in a model prohormone, mouse POMC (mPOMC) (Thorne, B. A., and Thomas, G. (1990) J. Biol. Chem. 265, 8436-8443. To investigate mechanisms of tissue-specific processing, we sought to identify the endoprotease signature of a cell having a processing phenotype distinct from insulinoma cells. In this report, the cleavage site specificity of the endoprotease(s) expressed in bovine adrenal chromaffin cells is examined. High levels of mPOMC (1.6 pmol/10(6) cells) were expressed in these cells using a vaccinia virus vector, and the precursor was targeted to the regulated secretory pathway. Analysis of POMC-derived peptides revealed that chromaffin cells processed the prohormone to a set of peptides highly similar to anterior pituitary corticotrophs, including adrenocorticotropin hormone (ACTH) and beta-lipotropin, gamma-lipotropin, and beta-endorphin. This processing contrasted with the pattern of cleavage site utilization in Rin m5F insulinoma cells, which more closely resembled that of the intermediate pituitary melanotrophs. However, the processing preference for the sequences of pairs of basic amino acids (as tested using the entire series of mutant cleavage sites; -LysArg- (native), -ArgArg-, -ArgLys-, -LysLys-, -HisArg-, -MetArg- at the ACTH/beta-lipotropin junction and -LysLys- (native), -LysArg-, -ArgArg-, -ArgLys- in beta-endorphin) was the same in both insulinoma and adrenal chromaffin cells, suggesting recognition and cleavage by similar enzymes in both cell types. The cell-specific processing of mPOMC may thus result from expression of a common core set of processing enzymes and factors unique to each cell type affecting the enzyme accessibility to precursor cleavage sites.
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PMID:Expression and processing of mouse proopiomelanocortin in bovine adrenal chromaffin cells. A model system to study tissue-specific prohormone processing. 185 97

The effect on endogenous beta-endorphins of a new synthetic protease inhibitor was studied in acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Plasma beta-endorphin concentrations and cardiovascular function were measured. Ten dogs (control group) were given 10 ml/kg/h of lactate Ringer's solution intravenously beginning 1 h before the induction of pancreatitis and continuing throughout the experiments. Six dogs received an intravenous infusion of 3 mg/kg/h of a new synthetic protease inhibitor, E-3123 (4-(2-succinimidoethylthio)4-geranidinobenzoate methanesuLfonate), in lactate Ringer's solution soon after the induction of pancreatitis. Plasma beta-endorphin concentrations in the control group increased significantly. However, plasma beta-endorphin levels in the protease inhibitor group did not increase as in the control group. The protease inhibitor infusion improved hypotension, myocardial depression, and plasma lactate, suggesting that the inhibitory effect of the protease inhibitor on beta-endorphin release contributed to the improvement.
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PMID:Effect of a new synthetic protease inhibitor on beta-endorphin release during acute pancreatitis in dogs. 187

Human peripheral blood mononuclear cells are analyzed for preproenkephalin gene expression and peptide processing. Met-enkephalin immunoreactivity as detected with a specific antiserum is found in the cytoplasm of monocytes but not in T lymphocytes. Secretion of met-enkephalin was analyzed with an RIA that is specific for the met-enkephalin pentapeptide. Unfractionated PBMC spontaneously released 40 pg/ml met-enkephalin and this increased two- to fourfold after stimulation with PHA. Lower levels (less than 100 pg/ml) of met-enkephalin were detected in supernatants from purified T cells that were activated with PHA and IL-2. In contrast, stimulation of purified monocytes with LPS or PMA resulted in the release of up to 600 pg/ml of the processed peptide. To examine whether T cells can produce met-enkephalin precursor peptides, T cell conditioned media were treated with trypsin and carboxypeptidase-B, which is known to release met-enkephalin from the propeptide. This increased levels of met-enkephalin to 400 pg/ml, indicating that lymphocytes secrete the propeptide but do not process it to met-enkephalin. The 1.4-kb preproenkephalin mRNA is detected in activated blood mononuclear cells and in purified monocytes and T cells. To determine whether monocytes or lymphocytes express met-enkephalin in vivo, lymphoid tissues were analyzed by immunohistochemistry. In human spleen tissue, positive cells were found in the red pulp but not in the follicles, which is also consistent with met-enkephalin expression in monocytes. In summary, these results show that human peripheral blood mononuclear cells express preproenkephalin mRNA and that monocytes, but not T cells, process the propeptide to metenkephalin.
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PMID:Differential processing of proenkephalin-A by human peripheral blood monocytes and T lymphocytes. 188 71

We have previously demonstrated an increase in plasma met-enkephalin levels during the pain attacks in episodic cluster headache. The present study was undertaken in order to clarify the source of the plasma met-enkephalin increase. Recent evidence has shown that peripheral blood polymorphonuclear cells contain peptides derived from the proenkephalin A system, which can be released by specific stimuli. We studied neutrophil met-enkephalin containing peptides (NMECP) in 27 episodic cluster headache patients: 24 in a cluster period (6 of them during a pain attack), and 3 in the remission period. Neutrophil met-enkephalin containing peptide levels (after sequential enzymatic digestion with trypsin and carboxypeptidase B) were determined by radioimmunoassay with specific antiserum. Neutrophil peptide concentration (pmol/mg prot) was lower (p less than 0.01) in patients during the pain attack (14.4 +/- 0.36) than after their pain had subsided (36.7 +/- 0.31) and lower than in the remission period patients (35.8 +/- 0.4). We conclude that neutrophil met-enkephalin containing peptides decrease during pain in episodic cluster headache, and that they may be involved in the concomitant plasma met-enkephalin increase.
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PMID:Changes in neutrophil met-enkephalin containing peptides in episodic cluster headache. 188 84

Previous immunochemical investigations have demonstrated various opioid peptides in the pancreas. However, controversies exist related to the cellular localization of these peptides in the endocrine pancreas. Therefore, the guinea pig endocrine pancreas was immunohistochemically investigated for the presence of opioid peptides derived from pro-dynorphin, pro-enkephalin or pro-opiomelano-cortin. Immunoreactivities were demonstrated on serial semithin sections by the peroxidase anti-peroxidase technique. In routinely immunostained sections, immunoreactivities for dynorphin A and alpha-neo-endorphin were localized in pancreatic enterochromaffin cells, but not in islet cells. Immunoreactivity for Met-enkephalin was confined exclusively to B-cells and was localized only in some secretory granules. However, pre-treatment of semi-thin sections with trypsin and carboxypeptidase B led to a marked increase of Met-enkephalin immunoreactivity in B-cells. In addition, immunoreactivities for Met-enkephalin-Arg-Gly-Leu and bovine adrenal medulla dodecapeptide could be demonstrated in B- and A-cells, and beta-endorphin immunoreactivity was localized in A-cells. In no case, however, were immunoreactivities detected for bovine adrenal medulla docosapeptide, peptide F, corticotropin, melanotropin or dynorphin 1-32. The immunohistochemical findings indicate that opioids of different peptide families are present in the guinea pig endocrine pancreas. Since several opioid peptides of the corresponding pro-hormones could be demonstrated in the reference organs but not in the pancreas, it is concluded that the biosynthetic pathways of the respective precursors are different from those in the adrenal medulla or in the pituitary.
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PMID:Immunohistochemistry of opioid peptides in the guinea pig endocrine pancreas. 197 Sep 50

Fast atom bombardment (FAB) mass spectrometry and multiple reaction monitoring (MRM) in the B/E linked-field scan mode were used to quantify endogenous beta-endorphin (BE) in individual human pituitary extracts. The experimental protocol includes the addition of a stable isotope-labeled internal standard ((2H4-Ile22)BE1-31, human) to the tissue homogenate before extraction, purification of the native BE by a combination of Sep-Pak chromatography and gradient high-performance liquid chromatography (HPLC), trypsin digestion to cleave BE into smaller peptides, and separation of the tryptic fragment BE20-24 (NAIIK) by isocratic reversed-phase HPLC. Mass spectrometric quantification is based upon recording either (a) the [M + H]+ ions of NAIIK and its deuterated analog ((2H4)NAIIK), or (b) the transitions ([NAIIK + H](+)----[NAI]+) and [((2H4)NAIIK + H](+)----[(2H4)NAI]+) using the B/E linked-field scan. Linear calibration curves were obtained using these two mass spectrometric techniques from standard solutions containing 1.25-20 micrograms of BE; each standard solution also contained 10 micrograms of (2H4)BE. The amounts (means +/- s.d.) of endogenous BE in five separate human pituitaries were found to be 156 +/- 84 [( M + H]+ method) and 169 +/- 99 pmol mg-1 protein (MRM method).
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PMID:Mass spectrometric quantification of endogenous beta-endorphin. 206 84

The influence of micelles of sodium dodecyl sulfate, cetyltrimethylammonium bromide, lysophosphatidylcholine and dodecylphosphorylcholine on the content and stability of the ordered structure of human beta-endorphin and its 12-26 fragment has been investigated. The structure was determined by far-ultraviolet circular dichroism and the stability by the resistance of the polypeptide to proteolysis with trypsin and chymotrypsin, monitored by HPLC. The alpha-helix inducing effects of the amphipathic compounds were in the order anionic greater than zwitterionic greater than cationic. The protection against proteolysis was very marked, especially for trypsin, and it was proportional to the alpha-helix inducing potential of amphipathic compounds. However, the lower resistance to proteolysis of the highly structured 12-26 fragment suggests that factors other than secondary structure may be responsible for the resistance to proteolysis.
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PMID:Circular dichroism and proteolysis of human beta-endorphin in surfactant and lipid solutions. 214 Dec 84


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