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)

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

At present our knowledge of enteric peptide-containing neurons in man is limited. In this study we have used human appendices removed at surgery to examine the peptidergic innervation by immunocytochemistry, immunochemistry, and pharmacological in vitro experiments. Immunocytochemistry revealed a variety of peptide-containing nerve fiber populations in the human appendix. VIP/PHI-, VIP/PHI/NPY-, SP/NKA-, galanin-, and enkephalin-containing nerve fibers were numerous; CGRP- and GRP-containing nerve fibers were moderate in number, while only scattered NPY-, enkephalin/BAM-, and somatostatin-containing nerve fibers could be found. No CCK-, dynorphin A-, or dynorphin B-immunoreactive nerve fibers could be detected. The coexistence of VIP/PHI, SP/NKA, and enkaphalin/BAM can be anticipated from the known sequence of their respective precursors. However, the coexistence of VIP/PHI and NPY was unexpected but corroborates previous observations in other species. Interestingly, SP and CGRP did not seem to coexist in nerve fibers of the human appendix. Immunochemistry (RIA and HPLC) confirmed the presence of VIP, NPY, SP, galanin, CGRP, GRP, enkephalin, and somatostatin. Motor activity studies suggest that acetylcholine plays a major role in the electrically evoked contractions, since atropine suppressed these contractions. Galanin (10(-8)-10(-6) M) and GRP (10(-9)-10(-7) M) caused concentration-dependent contractions that were unaffected by tetrodotoxin and thus probably reflect a direct action on smooth muscle receptors. GRP (10(-9) M) enhanced the electrically induced cholinergic contraction (to 193 +/- 24%), while met-enkephalin (10(-6) M) reduced it (to 54 +/- 6%). Both peptides failed to affect the contractile response to exogenous acetylcholine and probably act to modulate the release of acetylcholine. NPY, VIP, CGRP, SP, and somatostatin failed to induce contraction or to affect the electrically evoked contractions.
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PMID:Neuropeptides in the human appendix. Distribution and motor effects. 247 67

In segments of rabbit ear arteries preincubated with [3H]noradrenaline, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and ethylketocyclazocine concentration dependently reduced the overflow of tritium and the vasoconstriction elicited by field stimulation (120 pulses every 14 min, 1 Hz, 0.3 msec pulse duration). The effects of Leu-enkephalin and ethylketocyclazocine were antagonized by naloxone which, given alone, increased the evoked overflow of tritium at the high concentration of 10 microM. Morphine failed to produce inhibition, and at 100 microM actually increased evoked 3H-overflow. Continued exposure to Leu-enkephalin desensitized the tissue to this opioid; there was no cross-desensitization to ethylketocyclazocine. In arteries not preincubated with [3H]noradrenaline, normorphine, fentanyl and morphiceptin did not change the vasoconstrictor response (5 pulses every min, 5 Hz, 0.3 msec pulse duration). Among various peptide agonists, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and Met-enkephalin were the most potent inhibitors. In a series of peptides with C-terminal extensions of the Met-enkephalin chain, the potency decreased in the order Met-enkephalin greater than Met-enkephalin-Arg-Gly-Leu greater than Met-enkephalin-Arg-Phe greater than BAM-12P greater than beta-endorphin. In a series of peptides with C-terminal extensions of the Leu-enkephalin chain, the potency decreased in the order Leu-enkephalin greater than dynorphin1-13 greater than dynorphin1-9 greater than alpha-neo-endorphin greater than dynorphin1-8 greater than dynorphin1-6 greater than dynorphin1-17. The delta-selective antagonist ICI 154129 counteracted the effect of Met-enkephalin but not that of dynorphin1-13, whereas naloxone counteracted the effect of either agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Presynaptic opioid receptor subtypes in the rabbit ear artery. 298 15

The conversion of BAM-12P to Met-enkephalin and the hydrolysis of the Phe-Met and Phe-Leu bonds of met-enkephalin-Arg-Phe and Leu-enkephalin-Arg-Arg, respectively, by rabbit brain endo-oligopeptidase A were demonstrated. Peptide fragments were isolated by high performance liquid chromatography and identified by amino acid analysis. BAM 22P was not hydrolysed by the enzyme. The concentration dependent inhibition of BAM-12P conversion into Met-enkephalin by bradykinin and vice-versa provided additional evidence that endo-oligopeptidase A cleaves both the Phe5-Ser6 bond in bradykinin and the Met5-Arg6 bond of BAM-12P.
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PMID:Conversion and inactivation of opioid peptides by rabbit brain endo-oligopeptidase A. 299 91

Isolated tail arteries of rats were perfused and field-stimulated every 2 min with 2 pulses at 1 Hz. Different opioid peptides depressed the contractile responses to stimulation; their concentration-response curves showed a maximum at about 40% inhibition. The rank order of potency of the peptides was beta-endorphin (IC50 = 97 nmol/l) approximately equal to BAM-22P greater than FK-33824 greater than DAGO greater than [D-Ala2,D-Leu5]-enkephalin greater than or equal to metorphamide greater than dynorphin A-(1-13) approximately equal to [Met5]enkephalin. All these substances have in common a certain activity at opioid mu-receptors, although the enkephalins are preferential delta-, and the dynorphins preferential kappa-agonists. However, the selective delta-agonist [D-Pen2,L-Pen5]enkephalin was ineffective at up to 10 mumol/l, and the kappa-agonists ethylketocyclazocine and U-50488 acted only at concentrations higher than 3 mumol/l. Whereas the effects of beta-endorphin, DAGO and [D-Ala2,D-Leu5]enkephalin could be reduced by the mu-preferential antagonist naloxone, the effects of ethylketocyclazocine and U-50488 were not changed. The delta-selective antagonist ICI 174864 did not influence the action of [D-Ala2,D-Leu5]enkephalin. Naloxone in a concentration (1 mumol/l) which nearly abolished the effect of DAGO 3 mumol/l, slightly enhanced responses to stimulation. Neither beta-endorphin nor DAGO influenced vasoconstriction evoked by the application of noradrenaline or adenosine triphosphate; U-50488 reduced it. In arteries preincubated with [3H]noradrenaline DAGO depressed, whereas naloxone enhanced the tritium overflow and vasoconstriction evoked by field stimulation (0.4 Hz, 24 pulses every 14 min). In addition, naloxone antagonized the effect of DAGO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-endorphin-sensitive opioid receptors in the rat tail artery. 303 89

We have developed a method that is based on two HPLC systems and permits the separation of endogenous opioid peptides in tissue extracts. The individual peptides are bioassayed on the mouse isolated vas deferens; naloxone (100 nM) ensures opioid specificity. In the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine, the tissue content of prodynorphin-derived peptides is lower than those of proenkephalin-derived peptides. No beta-endorphin was detected. Of the prodynorphin fragments, alpha-neoendorphin, beta-neoendorphin, dynorphin A(1-8), and dynorphin B are present in equimolar concentrations (12-15 pmol/g) whereas the tissue content of dynorphin A is only 0.8 pmol/g. Processing of proenkephalin leads to at least six opioid peptides. The tissue contents of [Leu5]enkephalin, [Met5]enkephalyl-Arg-Gly-Leu, and [Met5]enkephalyl-Arg-Phe are 90-100 pmol/g and the content of [Met5]enkephalin is 405 pmol/g. BAM-18 and [Met5]enkephalyl-Arg-Arg-Val-NH2 are present in much lower concentrations, 24 and 5 pmol/g, respectively. Although present in low amounts, BAM-18 and [Met5]-enkephalyl-Arg-Arg-Val-NH2 have high affinity for the mu-opioid binding site and to a lesser extent for the kappa-site; this binding profile differs from that of the other proenkephalin fragments all of which have high affinities for the mu- and delta-sites.
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PMID:Tissue content of opioid peptides in the myenteric plexus-longitudinal muscle of guinea-pig small intestine. 337 12

Previous studies have shown that met- and leu-enkephalins are present in extracts of whole pancreas obtained from guinea pigs and human cadavers. The present studies demonstrate that immunoreactive methionine (met)- and leucine (leu)-enkephalins present in rat pancreas are localized in islets of Langerhans. Immunohistochemical staining of fixed, whole pancreas indicated that only islet endocrine cells were heavily stained when any of four different met- and leu-enkephalin-directed antisera or an anti-BAM-22P (bovine adrenal medulla docosapeptide) antiserum was used. The peptides were characterized by a combination of gel-filtration chromatography, high-performance liquid chromatography (HPLC), and specific radioimmunoassay. Free met-enkephalin content in extracts of rat islets was 90-fold enriched over content in extracts of whole pancreas (1.72 +/- 0.35 versus 0.019 +/- 0.007 pmol/mg protein). Treatment with trypsin and carboxy-peptidase-B of high-molecular-weight peptides extracted from pancreas or islets resulted in release of additional met-enkephalin immunoreactivity, which was 39-fold enriched in islets compared with pancreas (5.90 +/- 0.58 and 0.153 +/- 0.032 pmol/mg protein, respectively). Total islet content (per milligram protein) of met-enkephalin-containing peptides was similar to that reported elsewhere for bovine hypothalamus. The immunohistochemical data as well as the enrichment of extractable enkephalins in islets compared with whole pancreas indicate that essentially all the met-enkephalin present in pancreas is localized in islets, while the presence of BAM-22P immunoreactivity in islets is consistent with biosynthesis of enkephalins in islet cells via a preprohormone, such as that described in the bovine adrenal medulla and rat brain.
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PMID:Opioid peptides in rat islets of Langerhans. Immunoreactive met- and leu-enkephalins and BAM-22P. 351 Jan 38

We studied the secretion and tissue contents of adrenorphin in human pheochromocytomas. In 17 human pheochromocytomas from 11 patients, we found a remarkably wide distribution in immunoreactive adrenorphin levels (3-7771 pg/mg tissue). Adrenomedullary pheochromocytomas contained a significantly larger amount of immunoreactive adrenorphin (2295 +/- 1092 pg/mg, mean +/- SE) than did extramedullary ones (17.8 +/- 8.4 pg/mg). Gel chromatographic studies revealed that immunoreactive adrenorphin consisted largely of material emerging at the position of synthetic adrenorphin in both pheochromocytoma and normal adrenal medulla tissue. Nicotine (10(-5) M) significantly stimulated the secretion of immunoreactive adrenorphin as well as catecholamines from cultured human pheochromocytoma cells. Adrenorphin was a more potent inhibitor of catecholamine secretion evoked by 10(-5) M nicotine than was met-enkephalin in cultured human pheochromocytoma cells. The 50% inhibitory concentrations (IC50) were 1.1 X 10(-6) and 6.5 X 10(-5) M for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1-13) (IC50, 1.0 X 10(-6) M) and BAM-12P (IC50, 4.5 X 10(-6) M). These results indicate the presence and secretion of adrenorphin in human pheochromocytomas. Adrenorphin may play an important role in regulating catecholamine secretion in human pheochromocytoma.
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PMID:Studies on adrenorphin in pheochromocytoma. 381 99

The inhibitory activity of opioid peptides derived from pro-opiomelanocortin (POMC), pro-enkephalin A and pro-enkephalin B (= pro-dynorphin) on the electrically evoked twitch of the rat vas deferens (RVD) was evaluated. The POMC-derived beta-endorphin exhibits the greatest potency on this preparation. In addition, all peptides derived from pro-enkephalin A show full agonistic activity with BAM-22P and peptide E as the most potent peptides. In contrast, the majority of peptides derived from pro-enkephalin B (= pro-dynorphin) were essentially inactive on this tissue. Moreover, no antagonistic properties of these peptides were demonstrable in this preparation; thus the opioid receptors present in the RVD (putative epsilon receptors) might not possess any particular affinity for the pro-enkephalin B derived peptides.
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PMID:Opiate activity of peptides derived from the three opioid peptide families on the rat vas deferens. 609 92

The present paper describes the isolation and characterization of a clone of hybrid myelomas (3-E7) secreting a mouse monoclonal antibody to beta-endorphin. An examination of its specificity against a series of human beta-lipotropin fragments and other opioid peptides revealed that the N-terminus portion of beta-endorphin is the determinant. Complete or almost complete cross-reactivity was obtained to methionine- and leucine-enkephalin, beta-lipotropin 60-65, and BAM 22; partial cross-reactivity was seen to dynorphin1-13 and alpha-neo-endorphin, whereas beta-lipotropin, alpha-N-acetyl-beta-endorphin, Des-Tyr1-beta-endorphin, in addition to a series of synthetic enkephalin derivatives, completely lacked cross-reactivity. The use of the monoclonal antibody in radioimmunoassay (RIA) for beta-endorphin resulted in a lower sensitivity related to respective polyclonal antibodies. An increase of 100% in tracer binding could, however, be obtained by use of beta-endorphin iodinated with its N-terminal tyrosine protected by coupling to an antibody. A solid-phase RIA was developed involving the internally 3H-labeled monoclonal antibody, which resulted in a 10-fold increase in sensitivity as compared with the homogenous RIA. These data indicate that for the binding to this antibody a tyrosine residue in position 61 is essential, and it thus recognizes a site that is of functional significance for many naturally occurring opioid peptides.
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PMID:Binding characteristics of a monoclonal beta-endorphin antibody recognizing the N-terminus of opioid peptides. 618


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