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)

Oxytocin is secreted during parturition to stimulate myometrial contractions and birth. Prior to the start of labour, oxytocin neurones undergo changes to prepare for optimal secretion during labour. Thus, during late pregnancy oxytocin secretion is limited by endogenous opioid inhibition. This does not appear to act at the oxytocin nerve terminals in the neural lobe since they in fact become desensitised to opioid inhibition, responding less to either the general opioid antagonist, naloxone, or to the specific kappa-opioid agonist U50,488, and kappa-receptor binding decreases. However, removal of opioid inhibition on oxytocin neurones by naloxone activates oxytocin cell bodies and there is an increase in the number of cells expressing Fos protein in the supraoptic nucleus. This action is mediated via mu- and not kappa-opioid receptors since norBinaltorphimine (kappa-antagonist) is ineffective. Endogenous opioids are likely to act pre-synaptically on inputs to oxytocin neurones, especially those from the brainstem since naloxone potentiates the firing rate response of oxytocin neurones to intravenous cholecystokinin administration which acts via noradrenergic neurones. The endogenous opioid, beta-endorphin may be responsible for inhibition of oxytocin neurones as both the peptide content and its precursor proopiomelanocortin mRNA content increase in the arcuate nucleus during pregnancy, whereas expression of the co-localized opioids, prodynorphin or proenkephalin A, in magnocellular neurones does not alter.
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PMID:Pathways to parturition. 871 93

The biochemical and cellular mechanisms involved in the development and/or maintenance of morphine tolerance remain unclear. In the adult central nervous system (CNS) results are contradictory. For the neonate, a variety of drug induced deficits have been observed following prenatal addiction to opioids, although very little work on the biochemical and molecular level has been done. Therefore, the present study was carried out to investigate the effects of prenatal morphine treatment on the levels and expression of endogenous opioid peptides in brain regions of newborns. Dams were implanted with one morphine pellet (75 mg each) 1 week prior to the birth of pups. Changes in mRNA levels for the opioid peptides were determined by Northern blot analysis. Alterations in opioid peptide levels were determined by radioimmunoassays. Prenatal morphine treatment significantly increased proenkephalin mRNA levels and decreased met-enkephalin levels in striatum of newborns. These data are in contrast to what is observed in the adult CNS. These data indicate that prenatal morphine treatment may increase met-enkephalin release and/or cause inhibition at the level of translation. In addition, increased transcription may be necessary to maintain equilibrium in the system when there is an increase in met-enkephalin release.
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PMID:Prenatal morphine exposure differentially alters expression of opioid peptides in striatum of newborns. 875 Aug 81

The liver of adult rats with cholestasis secondary to bile duct resection has been shown to express the proenkephalin gene and, by immunohistochemical stains, to contain met-enkephalin. To further study hepatic opioids in cholestasis, concentrations of proenkephalin-derived endogenous opioids were measured in a rat model of cholestasis by the use of radioimmunoassays. The specificity of the immunoreactivity detected by the assays was confirmed by high performance liquid chromatography (HPLC). In adult male rats with cholestasis due to BDR, the concentrations of three proenkephalin-derived opioid peptides were increased. Specifically, the mean hepatic concentrations of met-enkephalin, Met-Enk-Arg6-Phe7 and leu-enkephalin were 2.5 (p < 0.005), 2.1 (p < 0.005) and 2.5 (p < 0.01) fold higher than the corresponding mean for controls. These findings provide further independent evidence that opioid peptides accumulate in the liver in a model of cholestasis and are consistent with de novo synthesis of opioid peptides occurring in the cholestatic liver. This phenomenon may have relevance to the altered function of the opioid system in cholestasis and to the role of the liver as a neuroendocrine organ.
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PMID:Hepatic concentrations of proenkephalin-derived opioids are increased in a rat model of cholestasis. 893 29

Injury to the sciatic nerve leads to the transganglionic degeneration of sensory axons and to the induction of neurotrophins and p75 nerve growth factor receptor synthesis by the denervated Schwann cells. Sciatic nerve axotomy caused a marked loss of substance P and of met-enkephalin in the lumbar cord. Substance P immunostaining and pre-proenkephalin mRNA expression were reduced in the dorsal horn layers I and II ipsilaterally to the lesion. Treating rats with low doses (0.25 mg/kg) of heparin or COS 8, a natural glycosaminoglycan mixture with low anticoagulant activity, the peptide loss was prevented and the content increased of about 50% above control values. The effects of COS 8 treatment were also evident on Schwann cells. COS 8 augmented the increase of nerve growth factor, brain-derived neurotrophic factor, and NT-3 mRNA expression in the distal stump of the axotomized sciatic nerve. Therefore, it can be concluded that glycosaminoglycans neuroprotective effects on lesioned sensory axons might have been mediated by the dramatic promotion of neurotrophin synthesis. Although the in vitro studies (Lesma et al.: J Neurosci Res, 1996) suggested also a likely direct effect as extracellular matrix components that is not mediated by trophic factors.
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PMID:Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors. 895 69

RESP18 (regulated endocrine-specific protein of 18 KD) is an endoplasmic reticulum (ER) protein that was identified by coordinate dopaminergic regulation with pro-opiomelanocortin in the rat neurointermediate pituitary. Many attributes of RESP18 suggest an important function in neuroendocrine cells. Several neuropeptides, growth factors, and enzymes involved in biosynthesis of classical chemical neurotransmitters, have been identified in germ cells, Sertoli cells, and spermatozoa. In this study, screening of reproductive tissues revealed high levels of RESP18 protein and mRNA in the testes but not in ovaries or epididymis. The testes and sperm expressed 18-KD RESP18 and a unique 19-KD isoform. To better understand RESP18 expression in the testes, we have examined the stages of the cycle of the seminiferous epithelium by immunohistochemistry and Western blot analyses. Immunohistochemical analysis showed that RESP18 protein was expressed exclusively in spermatocytes and maturing spermatids. RESP18 protein was expressed at high levels in Step 1-8 round spermatids, in which the PC4 prohormone convertase, nerve growth factor, and proenkephalin are also expressed. Western blots, Northern blots, and indirect immunofluorescence staining demonstrated RESP18 expression in sperm.
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PMID:Stage-specific expression of RESP18 in the testes. 898 41

Complex and contradictory data have been reported regarding the changes in spinal opioidergic systems associated with chronic inflammatory pain in the rat. In an attempt to solve these discrepancies, the in vivo release of met-enkephalin and dynorphin and the expression of the corresponding propeptide genes were investigated at the spinal level in arthritic rats and paired controls. A dramatic increase in the concentration of prodynorphin mRNA (+300-550%) and a less pronounced elevation of that of dynorphin-like material (+40-50%) were found in the dorsal part of cervical and lumbar segments of the spinal cord in rats rendered arthritic by an intradermal injection of Freund's adjuvant four weeks prior to these measurements. In addition, the spinal release of dynorphin-like material (assessed through an intrathecal perfusion procedure in halothane-anaesthetized animals) was approximately twice as high in arthritic rats as in controls. In spite of significant elevations in the levels of both met-enkephalin (+30-70%) and proenkephalin A mRNA (+40-50%) in the dorsal part of cervical and lumbar segments, the spinal release of met-enkephalin-like material was decreased (-50%) in arthritic rats as compared to paired controls. Proenkephalin A mRNA (but not prodynorphin mRNA) could be measured in dorsal root ganglia, and its levels were dramatically reduced in ganglia at the lumbar segments in arthritic rats. Such parallel reductions in the spinal release of met-enkephalin-like material and the levels of proenkephalin A mRNA in dorsal root ganglia of arthritic rats support the idea that the activity of primary afferent enkephalinergic fibres decreases markedly during chronic inflammatory pain.
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PMID:Enkephalinergic and dynorphinergic neurons in the spinal cord and dorsal root ganglia of the polyarthritic rat - in vivo release and cDNA hybridization studies. 907 Jun 23

Prohormone substrates are required for investigation of the proteolytic processing of prohormones and proproteins into active peptide hormones and neurotransmitters. However, the lack of prohormone proteins has been a limiting factor in elucidating proteolytic mechanisms for conversion of prohormones into active peptides. Therefore, in this study, cloned cDNAs encoding the prohormones proenkephalin (PE), pro-neuropeptide Y (pro-NPY), pro-opiomelanocortin (POMC), and beta-protachykinin (beta-PT) were utilized to express recombinant prohormones in Escherichia coli. High-level expression of milligrams of prohormones was achieved with the pET3c expression vector utilizing the T7 promoter for production of PE, pro-NPY, and POMC, as demonstrated by SDS-PAGE gel electrophoresis, Western blots, and 35S-methionine labeling. In addition, beta-PT was expressed at high levels as fusion proteins with the maltose-binding protein and glutathione S-transferase by the pMAL-c and pGEX-2T expression vectors, respectively. Relative rates of processing by the established processing proteases "prohormone thiol protease" (PTP), 70-kDa aspartyl protease, and PC1/ 3 and PC2 (PC, prohormone convertase) were examined with purified PE, pro-NPY, and POMC. Distinct preferences of processing enzymes for different prohormones was demonstrated. PTP preferred PE and pro-NPY substrates, whereas little processing of POMC was detected. In contrast, the 70-kDa aspartyl protease cleaved POMC more readily than pro-NPY or PE. However, PC1/3 and PC2 prefer POMC as substrate. Demonstration of selectivity of processing enzymes for prohormone substrates illustrates the importance of expressing recombinant prohormones for in vitro processing studies.
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PMID:High-level expression of the prohormones proenkephalin, pro-neuropeptide Y, proopiomelanocortin, and beta-protachykinin for in vitro prohormone processing. 917 94

The effect of [Met5]enkephalin, [Leu5]enkephalin, proenkephalin, dynorphin-(1-17) or beta-endorphin on the cytotoxic (51Cr release assay) activity of natural killer cells and macrophages/monocytes was studied in mice. It was found that a single i.p. injection of [Met5]enkephalin, [Leu5]enkephalin, beta-endorphin, dynorphin or proenkephalin as well as repeated treatment with both enkephalins increased natural killer cell activity. In vitro only [Met5]enkephalin stimulated natural killer cells. Opioid peptides did not affect the cytotoxic activity of macrophages/monocytes. In addition to functional alterations, both enkephalins and beta-endorphin increased the percentage of cells with natural killer phenotype. The results of this study suggest that the increase in natural killer cytotoxicity after opioid peptides injected once or for 14 days may result from an increased number of natural killer cells in the spleen.
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PMID:Effect of enkephalins and endorphins on cytotoxic activity of natural killer cells and macrophages/monocytes in mice. 919 78

Proenkephalin (Penk) gene expression is high in the adult hamster adrenal medulla and it is comparable to that found in both the hamster and rat striatum. In addition, Penk gene expression in the hamster adrenal medulla is more typical of adult mammalian adrenals than the rat. Since the nature of Penk gene expression in the developing hamster adrenal is not known, it was examined and compared to that found in the striatum were adult levels in the adrenal and striatum are similar. The results show that Penk gene expression progressively increases in the developing hamster adrenal to peak on postnatal day 4. There is then a small decline to adult levels by postnatal day 12 when the morphology of the developing adrenal resembles the adult. Functional splanchnic nerve activity, as assessed by the ability of reserpine to induce increases in adrenal tyrosine hydroxylase mRNA, is not present until after postnatal day 4. Therefore, early increases in Penk gene expression are independent of splanchnic nerve activity. Adrenal EC peptides resulting from the developmental increases in Penk gene expression appear to be unprocessed and proenkephalin-like. This is based on the very low levels of free enkephalin (met-enkephalin) detected in the adrenals from both newborn and adult hamsters (1-5% of total EC peptide levels). In the developing hamster striatum, Penk gene expression remains low and unchanged until postnatal day 4 and increases six-fold by adulthood. Free enkephalin (met-enkephalin) levels remain high (between 36 and 88% of total EC peptide levels) in the developing and adult hamster striatum. Therefore the results show early increases in adrenal Penk gene expression in the developing hamster that are independent of splanchnic nerve activity and adult Penk gene expression which is high and dependent on splanchnic nerve activity. This differs from what is observed in the frequently studied rat. However, developmental changes in the hamster striatum are similar to those in the rat.
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PMID:Changes in proenkephalin gene expression in the developing hamster. 926 96

We investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
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PMID:T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. 935 52


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