Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study focuses on the involvement of catecholamines and nine different peptides in efferents of the nucleus of the solitary tract to the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and different parabrachial and hypothalamic nuclei in the rat. A double-labeling technique was used that combines a protein-gold complex as the retrograde tracer with immunohistochemistry. Catecholaminergic projection neurons were the most numerous type observed and projected mainly ipsilaterally to all targets studied. Most projections arose from areas overlying the dorsal motor nucleus, mainly the medial nucleus. Neurons synthesizing somatostatin, met-enkephalin-Arg-Gly-Leu, dynorphin B, neuropeptide Y, and neurotensin projected to all structures examined. Somatostatin and enkephalin immunoreactive projection cells were the most numerous. They were located in close proximity to each other, including all subnuclei immediately surrounding the solitary tract, bilaterally. Most dynorphin and neuropeptide Y immunoreactive projection cells were found rostral to that of enkephalinergic and somatostatinergic projections, and mainly in the ipsilateral medial nucleus. Neurotensinergic projections were sparse and from dorsal and dorsolateral nuclei. Substance P and cholecystokinin contribute to parabrachial afferents. The location of substance P immunoreactive projection cells closely resembled that of enkephalinergic and somatostatinergic projections. Projecting cholecystokinin immunoreactive cells were observed in dorsolateral nucleus. Bombesin immunoreactive cells in dorsal nucleus projected to either the parabrachial or hypothalamic nuclei. No vasoactive intestinal polypeptide-containing cells were detected. Thus, most catecholaminergic and neuropeptidergic efferents originated from different populations of cells. It is proposed that catecholaminergic neurons constitute the bulk of solitary efferents and that they may contribute to autonomic neurotransmission. Peptidergic neurons mainly form other subgroups of projections and may play a role in modulating the physiological state of the target nuclei.
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PMID:Neuropeptides and catecholamines in efferent projections of the nuclei of the solitary tract in the rat. 196 68

Our observations that opioid peptides have direct effects on islet insulin secretion and liver glucose production prompted a search for endogenous opiates and their receptors in these peripheral tissues. Mu-, delta- and kappa-receptor-active opiates were demonstrated in brain, pancreas and liver extracts by displacement studies using selective ligands for the three opiate receptor subtypes [( 3H][D-Ala2,MePhe4,Gly5-ol]enkephalin, [3H][D-Ala2,D-Leu5]enkephalin and [3H]dynorphin respectively). Receptor-active opiates in brain extracts exhibited a stronger preference for delta-opiate-receptor sites than for mu and kappa sites. Pancreatic extract opiates demonstrated a similar activity at mu and delta sites, but substantially less at kappa sites. Liver extracts displayed similar selectivity for all three sites. The affinities of the receptor-active opiates for mu-, delta- and kappa-receptor subtypes displayed a rank order of potency: brain much greater than pancreas greater than liver. Total immunoreactive beta-endorphin and [Met5]enkephalin levels in liver and hepatocytes were greater than those in brain. Immunoreactive [Met5]enkephalin levels in pancreas were similar to, but beta-endorphin levels were substantially higher than, those in brain. Delta and kappa opiate-binding sites of high affinity were identified in crude membrane preparations of islets of Langerhans, but no specific opiate-binding sites could be demonstrated in liver membrane preparations. Immunoreactive dynorphin and beta-endorphin were demonstrated by immunogold labelling in rat pancreatic islet cells. No positive staining of liver sections for opioids was observed. These results suggest that the tissue content of opiate-receptor-active compounds in the pancreas and the liver is very significant and could contribute to the regulation of normal blood glucose levels.
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PMID:The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain. 197 Feb 40

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

The hypothalamus is a major source of afferents to the parabrachial nucleus (PB), but the neurotransmitters in this pathway are largely unknown. In this study, we examine the neuropeptide immunoreactivities of neurons in the hypothalamus that project to the PB by using the combined retrograde fluorescence-immunofluorescence method. After injections of the fluorescent tracer fast blue into the PB, retrogradely labeled neurons were observed in the paraventricular, dorsomedial, ventromedial, median preoptic, and anteroventral periventricular hypothalamic nuclei; in the dorsal, retrochiasmatic, and lateral hypothalamic areas; and in the medial and lateral preoptic areas. Our results show that at least five distinct neuropeptide-immunoreactive cell populations in the hypothalamus project to the PB. In the perifornical lateral hypothalamus, many neurotensin (NT)-, corticotropin-releasing factor-, dynorphin (DYN)-, angiotensin II (AII)-, and galanin-like immunoreactive (-ir) neurons were retrogradely labeled. A cluster of retrogradely labeled neurons in the juxtacapsular lateral hypothalamus stained with an antiserum against alpha-melanocyte stimulating hormone (alpha MSH). Over 50% of the retrogradely labeled cells in the arcuate nucleus were adrenocorticotropin (ACTH)-or alpha MSH-ir. Many alpha MSH- and ACTH-ir, and a few DYN-, NT- and AII-ir neurons in the retrochiasmatic area were retrogradely labeled. Only small numbers of double-labeled neurons were found in the paraventricular nucleus, and, of these, enkephalin-ir and dynorphin-ir neurons were the most common. Somatostatin-ir cells in the hypothalamus were rarely double-labeled. The chemical coding of these hypothalamic projections to the PB may provide important clues to the functional organization of these descending pathways.
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PMID:Neuropeptide organization of the hypothalamic projection to the parabrachial nucleus in the rat. 197 10

We performed immunohistochemical analysis of specimens from three autopsied patients with Parkinson's disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinson's disease.
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PMID:Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. 197 53

The antianalgesic effect of dynorphin A (1-17) (dyn A) was demonstrated by i.c.v. administration of agonists (morphine, Tyr-D-Ala2-Gly-N-MePhe4-Gly-ol5, D-Pen2-D-Pen5-enkephalin, beta-endorphin, U50,488H and physostigmine) at 10 min and intrathecal administration of dyn A at 5 min before the tail-flick test in mice. This antianalgesic effect of dyn A was eliminated by 3 or 5.5 hr pretreatment s.c. with 10 or 100 mg/kg of morphine, respectively. This desensitization lasted for about 18 hr. Three-hour pretreatment intrathecally with dyn A also desensitized the mice to dyn A. Previously we had shown that i.c.v. administration of morphine simultaneously activates analgesic and antianalgesic systems and the latter is mediated spinally by dyn A, an endogenous antianalgesic opioid. Present results are consistent with that concept and systemic pretreatment with morphine may release dyn A in the spinal cord to produce the desensitization to the subsequently elicited antianalgesic action of dyn A.
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PMID:Systemic single dose morphine pretreatment desensitizes mice to the spinal antianalgesic action of dynorphin A (1-17). 197 92

Effects of the glucocorticoid milieu on the basal and ether stress-induced prolactin (PRL) release and on the immunostaining for hypothalamic vasoactive intestinal peptide (VIP), beta-endorphin (beta-EP), dynorphin-A (DYN-A) and methionine-enkephalin (Met-ENK), were examined in separate groups of male rats. After colchicine treatment in intact rats, VIP-containing cell bodies were observed only in the suprachiasmatic nucleus (SCN). Adrenalectomy (ADX), performed 7 days previously, resulted in the additional appearance of VIP-immunoreactive neurons in the parvocellular subdivision of the paraventricular nucleus (PVN), as well as in significantly higher basal and stressed PRL levels than intact values. Treatment of intact rats with a high dose (500 micrograms/kg body weight (s.c.) daily for 7 days) of dexamethasone (DEX), but not with a low dose (50 micrograms/kg) of DEX, significantly reduced both the basal and stressed PRL release. Administration of either the low or high dose of DEX to ADX rats prevented the appearance of the PVN-VIP neurons. In addition, the ADX-induced high basal and stressed PRL levels were restored to intact values by the low dose of DEX, and completely suppressed by the high dose of DEX. The staining of SCN-VIP-, beta-EP-, DYN-A or Met-ENK neurons was not affected by any treatment employed in this study. These results suggest that the appearance of PVN-VIP immunostaining in ADX rats may, at least in part, be responsible for the enhanced PRL secretion observed in this group. However, SCN-VIP-, beta-EP-, DYN-A- or Met-ENK neurons do not seem to play a pivotal role in the glucocorticoid regulation of PRL secretion.
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PMID:The immunostaining for the hypothalamic vasoactive intestinal peptide, but not for beta-endorphin, dynorphin-A or methionine-enkephalin, is affected by the glucocorticoid milieu in the rat: correlation with the prolactin secretion. 197 81

Two peptide models of dynorphin A(1-17) have been synthesized. These peptides incorporate a minimally homologous substitute sequence for residues 6-17, including alternating lysine and valine residues substituting for the potential amphiphilic beta-strand structure in positions 7-15. Model 1 retains Pro10 from the native sequence, but model 2 does not. Compression isotherms of peptide monolayers at the air-water interface and CD spectra of peptide films adsorbed from aqueous solution onto siliconized quartz slides were evaluated by comparison to those of idealized amphiphilic alpha-helical, beta-sheet, and disordered peptides. Dynorphin A(1-17) was mostly disordered, whereas beta-endorphin was alpha helical. Dynorphin model 1 had properties similar to those of dynorphin A(1-17) at these interfaces, but model 2 formed strongly amphiphilic beta sheets. In binding assays to mu-, delta-, and kappa-opioid receptors in guinea pig brain membranes, model 1 reproduced the high potency and selectivity of dynorphin A(1-17) for kappa receptors, and model 2 was only 3 times less potent and less selective for these receptors. Both peptide models retained the high, kappa-selective agonist activity of dynorphin A(1-17) in guinea pig ileum assays, and like dynorphin A(1-17), model 1 had little activity in the rat vas deferens assay. In view of the minimal homology of the modeled dynorphin structures, these studies support current models of membrane-catalyzed opioid ligand-receptor interactions and suggest a role for the amphiphilic alpha-helical and beta-strand structures in beta-endorphin and dynorphin A(1-17), respectively, in this process.
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PMID:Peptide models of dynorphin A(1-17) incorporating minimally homologous substitutes for the potential amphiphilic beta strand in residues 7-15. 197 58

Earlier studies from this laboratory indicated that intracerebroventricular administration of physostigmine and clonidine activated both a spinal descending analgesic and antianalgesic system. It was proposed that the latter was mediated spinally by dynorphin A (1-17), because small intrathecal doses (fmol) of dynorphin A (1-17) antagonized analgesia, while intrathecal administration of naloxone and nor-binaltorphimine (at doses which had no effect on spinal mu and kappa receptors) enhanced analgesia by attenuating the antianalgesic component. In the present studies in mice, using the tail-flick response, intrathecal administration of dynorphin antibody (antiserum to dynorphin) enhanced the analgesic effect of (10 min) physostigmine and clonidine given intraventricularly. Peak effect for the antiserum was at 1 hr. Inhibition of the tail-flick response, induced by DAMGO (Tyr-D-Ala2-Gly-NMePhe4-Gly-ol5, a mu agonist), U50, 488 H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate hydrate, a kappa agonist) and morphine was also enhanced by intrathecal administration of dynorphin antiserum. Thus, a variety of analgesic agonists appear to activate a dynorphin-mediated antianalgesic system. Such a system appears not to be activated by intraventricular administration of beta-endorphin and DPDPE (D-Pen2-D-Pen5-enkephalin, a delta agonist) because neither beta-endorphin- nor DPDPE-induced analgesia was enhanced by intrathecal administration of antiserum. The results of the experiments with the antibody provide further evidence to support the role of dynorphin A (1-17), as a putative endogenous opioid, which mediates an antianalgesic descending system in the spinal cord.
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PMID:Spinal dynorphin A (1-17): possible mediator of antianalgesic action. 197 11

E2078, a new analgesic is a dynorphin derivative. E2078 shows strong affinity to kappa receptors and is not rapidly cleaved by peptidases. This analgesic is also considered to be free of tolerance and dependence. In the present study, to determine the effect of E2078 on pituitary-adrenocortical function the author administered E2078 (0.001, 0.05, 0.1, 1.0, 10.0 mg.kg-1) by intramuscular injection to 38 adult mongrel dogs under enflurane anesthesia (1.0%) and then investigated the changes in the plasma concentrations of ACTH, cortisol, beta-endorphin, PRA, aldosterone and ADH. In the animal groups which received E2078 at dosages of 0.001, 0.05, 0.1, and 1.0 mg.kg-1, no significant differences in the plasma concentrations of each hormone were detected compared with the control group which received physiological saline by intramuscular injection. However, in the dog group which received E2078 at 10.0 mg.kg-1, the plasma concentrations of PRA and aldosterone were significantly elevated.
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PMID:[Effects of E2078, a new dynorphin derivative, on pituitary-adrenocortical functions in dogs]. 197 31


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