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)

Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. We have determined that greater than 70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. Oligosaccharides terminating with this sequence have previously been described on lutropin, thyrotropin, and pro-opiomelanocortin: glycoproteins synthesized in the anterior pituitary. A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4-sulfotransferase accounts for the addition of sulfate. The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI.
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PMID:The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha. 138 66

Calcitonin gene-related polypeptide (CGRP) was purified from ovine hypothalamic extracts. Its amino acid sequence was determined as: Ser-(Cys)-Asn-Thr-Ala-Thr-(Cys)-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser - Gly-Gly-Val-Val-Lys-Ser-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Gln-Ala-Phe- NH2. This sequence differs from rat CGRP by two amino acid substitutions (Ser for Asp25 and Gln for Glu35). Adenylate cyclase stimulating activity in rat pituitary cell cultures was monitored during the isolation. CGRP had adenylate cyclase stimulating activity comparable to corticotropin-releasing hormone, suggesting a hypophysiotropic role for CGRP. This is the first chemical characterization of CGRP in the brain (hypothalamus).
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PMID:Identification of calcitonin gene related peptide in ovine hypothalamic extract. 141 24

Receptor-mediated binding of leukocyte chemotactic peptide, N-formylMet-Leu-Phe (fMLP), occurs in the ciliated protozoon Tetrahymena thermophila. In vivo labelling of the cells with N-formylMet-Leu-[3H]Phe ([3H]fMLP) shows that the cells bind the ligand with high affinity (KD = 4 x 10(-9) M to 1 x 10(-8) M). Moreover, Scatchard transformations of the binding data show that there are about 5 x 10(5) binding sites per cell on the cell surface. Two fluorescent derivatives of leukocyte chemotactic peptide, N-dansylMet-Leu-Phe (dansMLP) and N-formylMet-Leu-Phe-(N-dansyl-)Lys (fMLPdanLys) compete for the N-formylMet-Leu-Phe (fMLP) binding sites on the cell surface. Moreover, both derivatives have retained significant chemoattracting potentials. Fluorescence from dansMLP, but not from fMLPdansLys and dansyl-beta-endorphin, is internalized preferentially into small vesicles. The differences may, however, reflect that the fluorescence from the dansyl group is strongly quenched by a hydrophilic microenvironment when using the two latter peptide derivatives. In contrast, the dansyl group from dansMLP must be assumed to be embedded in a hydrophobic microenvironment in the vesicular membrane or membrane protein. Rhodamine-labelled bovine serum albumin, egg albumin and cytochrome c as well as dansylated bovine serum albumin, which are poor chemoattractants, are preferentially seen to be internalized into large vesicles (food vacuoles).
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PMID:Chemotactic properties, cellular binding and uptake of peptides and peptide derivatives: studies with Tetrahymena thermophila. 147 55

The release of the neuropeptide Met-enkephalin (Met-ENK) from isolated nerve terminals (synaptosomes) of the rat forebrain was characterized with respect to the subcellular distribution, the release upon addition of various stimulatory agents, the release kinetics, the cation-dependence of release and the relationship between Met-ENK release and elevations of the intraterminal free Ca(2+)-concentration ([Ca]i). A highly specific radioimmunoassay was developed for determination of Met-ENK (H-Tyr-Gly-Gly-Phe-Met-OH). Truncated and elongated forms of Met-ENK, Leu-enkephalin, beta-endorphin and dynorphin displayed negligible cross-reactivity. Met-ENK-like immunoreactivity (Met-ENK-LI) is enriched in the purified synaptosomal fraction of rat forebrain homogenates and is released in a strictly Ca(2+)-dependent manner upon chemical depolarization or stimulation with the Ca2+ ionophore, ionomycin. A correlation exists between the release of Met-ENK-LI and the elevations of [Ca]i. Barium ions are able to replace Ca2+ in triggering Met-ENK-LI release. The release of Met-ENK-LI is initiated within 20 s after depolarization and is terminated after 3-5 min, although depolarization and [Ca]i elevation are maintained. At this time, > 90% of the initial Met-ENK-LI is still present inside the synaptosomes. Repolarization and renewed stimulation again evokes Ca(2+)-dependent release of this retained Met-ENK-LI. It is concluded that Met-ENK release from isolated nerve terminals is exocytotic, and that exocytosis is terminated by a regulatory mechanism in synaptosomes after 3-5 min of depolarization, a process which can be reversed by repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the release of Met-enkephalin from isolated nerve terminals: release kinetics and cation-dependence. 148 89

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
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PMID:Neurochemical effects of vagus nerve stimulation in humans. 150 37

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.
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PMID:Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase). 152 Feb 71

The possible existence of a feedback control by endogenous opioids of the spinal release of met-enkephalin-like material was assessed in vivo, in halothane-anesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid-related drugs. Both the intrathecal perfusion of the mu agonist D-Ala2-D-MePhe4-Gly-ol5-enkephalin (DAGO) (10 microM) and the delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (10 microM) produced a significant inhibition of the spinal outflow of met-enkephalin-like material. The effect of DAGO, but not that of DTLET, could be prevented by naloxone (10 microM), and, conversely, the effect of DLTET, but not that of DAGO, was no longer observed in the presence of naltrindole (10 microM). Therefore naloxone and naltrindole acted as potent and selective mu and delta antagonists, respectively, when perfused at 10 microM in the intrathecal space of halothane-anesthetized rats. As expected from the lack of a tonic opioid control of spinal enkephalinergic neurones, neither naloxone nor naltrindole alone affected the spontaneous outflow of met-enkephalin-like material. However, naltrindole, but not naloxone, markedly increased the spinal overflow of met-enkephalin-like material due to intrathecal administration of either porcine calcitonin (10 microM) or the peptidase inhibitors thiorphan (10 microM) plus bestatin (20 microM). These data suggest that delta, but not mu, receptors are involved in a phasic opioid inhibitory control of the release of met-enkephalin-like material in the rat spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Feedback inhibition of met-enkephalin release from the rat spinal cord in vivo. 160 25

The binding and internalization of a novel adrenocorticotropic hormone (ACTH) analog having a potent neuromodulating effect, ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), by isolated bovine brain capillaries, were examined. Metabolism of [5-125I-His]ebiratide occurred during a 30-min incubation with bovine brain capillaries at 37 degrees C. In the presence of 20 mM EDTA, added to inhibit this metabolism, the medium, after 30 min of incubation, contained 82.3 +/- 0.5% of the unchanged ebiratide. The total binding and acid-resistant binding of [125I]ebiratide increased with time and reached an equilibrium at about 15 min. The total binding and acid-resistant binding at 30 min (as the cell/medium ratios corrected with [14C]sucrose) were 13.07 +/- 0.86 and 5.00 +/- 0.18 microliters/mg of protein, respectively. The acid-resistant binding showed significant dependence on temperature and medium osmolarity. The [125I]ebiratide binding was significantly inhibited by dansylcadaverine, an endocytosis inhibitor. The saturable acid-resistant binding was obtained by the addition of unlabeled ebiratide (100 nM-5 mM), and the maximal internalization capacity (Bmax) at 30 min was 144.2 pmol/mg of protein, with the half-saturation constant (KD) of 62.1 microM. The nonsaturable acid-resistant binding [cell/medium ratio in the presence of the unlabeled compound (1 mM or more)] was 2.2 microliters/mg of protein. The acid-resistant binding was significantly inhibited by human ACTH, poly-L-lysine, protamine and E-2078, a basic peptide, but was not inhibited by poly-L-glutamate, insulin or transferrin. These results demonstrate that ebiratide is transported through the blood-brain barrier via a basic peptide-specific absorptive-mediated endocytosis.
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PMID:Transport mechanism of a new behaviorally highly potent adrenocorticotropic hormone (ACTH) analog, ebiratide, through the blood-brain barrier. 165 Aug 27

Adrenocorticotropic (ACTH) and melanocyte stimulating (MSH) hormones have been demonstrated in the same cells in the cephalic half of the pars distalis of the chicken pituitary glands in three ways: (I) immunohistochemistry, (II) radioimmunoassay (RIA) using both anti-human or porcine ACTH and synthetic alpha-MSH antibodies, and (III) isolation and purification, followed by the determination of amino acid compositions of both hormones. The contents of ACTH and alpha-MSH are estimated by RIA to be 1600 and 10 ng/gland, respectively. ACTH missed 1 (des-Phe39-ACTH) or 2 residues (des-Glu38, Phe39-ACTH) from the C-terminal portion was also isolated. The recoveries of these ACTHs are differed from preparation to preparation. The complete amino acid sequence of chicken ACTH (39 residues) has been determined as NH2-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Arg-Lys-Arg- Arg- Pro-Ile-Lys-Val-Tyr-Pro-Asn-Gly-Val-Asp-Glu-Glu-Ser-Ala-Glu-Ser-Tyr-Pro- Met-Glu-Phe-OH Strikingly the amino acid sequence of chicken ACTH shows a closer resemblance to that from an amphibian, Xenopus (3 residue substitution) than that from another bird, the ostrich (7 residue substitution) or the turkey (at least 9 residue substitution).
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PMID:Characterization of chicken ACTH and alpha-MSH: the primary sequence of chicken ACTH is more similar to Xenopus ACTH than to other avian ACTH. 165 32

Bremazocine, a benzomorphan, has been reported to have kappa, mu and epsilon opioid receptor binding activities. The present studies were then designed to determine what types of opioid receptors and neurotransmitters were involved in inhibiting the tail-flick response induced by bremazocine in male ICR mice. U50, 488H, a prototypic kappa agonist, was used for comparison. Bremazocine, at doses from 0.1 to 1 microgram given i.c.v., dose-dependently inhibited the tail-flick response. The paw-licking hot plate response, even at high doses of bremazocine, was not completely inhibited. The inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. was blocked by i.c.v. coadministration of beta-endorphin-(1-27) (3 and 6 micrograms), an epsilon opioid receptor antagonist and norbinaltorphimine (4 micrograms), a kappa opioid receptor antagonist. On the other hand, the inhibition induced by i.c.v. U50,488H (40 micrograms) was blocked by i.c.v. norbinaltorphimine, but not beta-endorphin-(1-27). D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP; 0.5 microgram) and beta-funaltrexamine (beta-FNA; 2.5 micrograms), selective mu opioid receptor antagonists, and ICI 174,864 (10 micrograms), a delta-opioid receptor antagonist, which blocked the effects induced by DAMGO (16 ng) and DPDPE (20 micrograms), respectively, did not block inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. The inhibition of the tail-flick response induced by i.t. administration of bremazocine (1 microgram) was blocked by i.t. coadministration of norbinaltorphimine but not CTOP, ICI 174,864, or beta-endorphin-(1-27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of epsilon and kappa opioid receptors in inhibition of the tail-flick response induced by bremazocine in the mouse. 165 27


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