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)

Studies in the experimental mouse pituitary tumor cell line AtT-20/D-16-v have recently shown that ACTH, the lipotropins (beta- and gamma-LPH), beta-endorphin (beta-End) and the 16-K fragment are synthesized through a common precursor molecule which is a 31,000 glycopeptide (pro-ACTH/endorphin). We have investigated whether such a biosynthetic model might exist in man. Radioimmunoassays have been developed against human ACTH, N-terminal LPH, beta-End or C-terminal beta-LPH, C-terminal gamma-LPH, and the 16-K fragment or N-terminal pro-ACTH/endorphin. These radioimmunoassays were used to examine various human samples before and after gel fractionation in ordinary or denaturing buffers. Medium DMS-79, in which human small cell carcinoma cells derived from a lung cancer were cultured, was shown to contain molecules identical to gamma-LPH, beta-LPH, beta-End and ACTH. In addition, it also contained a high molecular weight material with LPH, beta-End, and ACTH immunoreactivity. These three immunoreactivities could not be dissociated under denaturing conditions (6 M guanidine-HCl), and were all absorbed on an ACTH-purified anti-(1-24)-ACTH affinity column. Medium DMS-79 also contained high molecular weight calcitonin immunoreactivity that was not absorbed on the (1-24)-ACTH affinity column and therefore was not part of the pro-ACTH/endorphin molecule. Extracts from two pheochromocytomas responsible for the ectopic ACTH syndrome were found to contain, in addition to ACTH, large amounts of gamma-LPH and beta-End. High levels of beta-LPH and beta-End were also present in the plasma from a patient with the ectopic ACTH syndrome due to pancreatic carcinoma. Plasma immunoreactive 16-K fragment was increased in another patient with this syndrome. These results indicate that a biosynthetic model similar to that described in the AtT-20/D-16-v mouse tumor cell line also exists in man. Tumors responsible for the ectopic ACTH syndrome provide a unique source to study this model in man.
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PMID:[Ectopic secretion of ACTH and of related peptides (LPHs, beta-endorphin, "16K"). Evidence for a common precursor]. 626 15

Extracts of human term placenta were fractionated by Sephadex G-75 gel filtration and assayed for immunoreactive ACTH. Both high and low molecular weight protein fractions were detected to be immunologically reactive toward anti-human ACTH (1--39 alpha) antibody. For the extraction of low molecular weight ACTH from human term placenta (pl. -ACTH), a glacial acetic acid-acetone mixture was employed, while a pH 3.0-HCl solution was used for high molecular weight immunoreactive ACTH. The high molecular weight immunoreactive ACTH fraction (F-I), co-eluted with horse hemoglobin from a Sephadex G-75.column in 0.1M acetic acid, was essentially devoid of low molecular weight materials as revealed by polyacrylamide gel disc electrophoresis at pHs 9.5 and 4.3. Tryptic digestion of F-1 at pH 8.1 and 37 degrees C for 4 hr with E/S of 1/100, followed by fractionation with a Sephadex G-75, resulted in the formation of lower molecular weight fragments. One fragment was eluted at the same position as that of porcine ACTH with a recovery of 86% of immunoreactivity of F-I. Another fragment which was eluted last exhibited positive beta-endorphin receptor binding activity. These results suggest the presence of a common precursor protein to ACTH and beta-endorphin in human term placenta.
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PMID:[Studies on immunoreactive ACTH from human term placenta. (I) Detection of a high molecular weight-immunoreactive ACTH in term placenta (author's transl)]. 626 17

The effects of intraventricular (i.v.t.) morphine sulfate (MS) and beta-endorphin (beta-EP) on pituitary-adrenal activity and the release of pituitary beta-EP were studied in rats. Pituitary-adrenal activity was monitored by measuring plasma corticosterone (CS) levels. 45 min after i.v.t. injection, both MS and beta-EP caused dose-related increases in plasma CS, with beta-EP being approximately ten times more potent on a molar basis. MS injected i.v.t. at 0.3, 1.0, 3.0 and 10.0 microgram did not cause a significant reduction in pituitary immunoreactive (i.r.) beta-EP, but did cause an increase in plasma i.r. beta-EP at 3 microgram of MS. beta-EP injected i.v.t. at 1.5 microgram caused a reduction of pituitary i.r. beta-EP. Since i.v.t.-injected beta-EP may have contributed to the measured plasma i.r. beta-EP, a nonimmunoreactive analog (Des-Asn20-beta c-EP) was used to assess the change in plasma i.r. beta-EP. 5 microgram of DES-Asn20-beta c-EP injected i.v.t. caused increases in plasma i.r. beta-EP and CS, as well as a 40% reduction in pituitary i.r. beta-EP. The concomitant intraperitoneal (i.p.) injection of naloxone HCl (10 mg/kg) significantly blocked the increase in plasma CS induced by 5 microgram of beta-EP. When naloxone HCl, 10 mg/kg was injected alone, a significant increase in plasma CS was found. The results indicate that i.v.t. beta-EP is more potent than MS in causing the release of pituitary ACTH and beta-EP. These findings are consistent with a role for brain endorphins in the regulation of CRF release.
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PMID:Effect of intraventricular beta-endorphin and morphine on hypothalamic-pituitary-adrenal activity and the release of pituitary beta-endorphin. 627 May 85

Combined rostral, median and neurointermediate lobes from 650 pituitary glands of the dogfish Squalus acanthias were extracted in 0.1 M-HCl and subjected to filtration on Sephadex G-50. Fractions were monitored for ACTH, alpha-MSH, gamma-MSH and endorphin by heterologous radioimmunoassay, corticotrophin-like intermediate lobe peptide (CLIP) and gamma-MSH by homologous radioimmunoassay, and methionine enkephalin after enzymatic digestion. The majority (about 99%) of the immunoreactivity detected was present as small peptides, with alpha-MSH, CLIP and gamma-MSH predominant. The single peaks of ACTH, alpha-MSH and CLIP contrasted with many distinct peaks of endorphin-like immunoreactivity. The gamma-MSH radioimmunoassays monitored different peptides; the heterologous assay revealed a single major peak, while the homologous assay detected a number of distinct small peptides. The results suggested that there may be more than three distinct forms of MSH in the dogfish pituitary gland. Small amounts of much larger proteins were detected by a number of the radioimmunoassays, suggesting that peptides related to ACTH, gamma-MSH and lipotrophin are derived from common pro-opiocortin-type precursor molecules in this phylogenetically ancient cartilaginous fish.
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PMID:Peptides derived from pro-opiocortin in the pituitary gland of the dogfish, Squalus acanthias. 628 8

Neurosecretory granules (NSGs) from neural lobes of bovine pituitary glands were isolated in a highly purified form by metrizamide-sucrose gradient centrifugation. The purified NSGs were lysed and centrifuged, and the supernatants were further fractionated by gel filtration on Sephadex G-75. Proopiocortin-converting enzyme activity was assayed by incubation of [3H]arginine- or [3H]phenylalanine-labeled toad proopiocortin with NSG supernatant fractions. The processed products were identified by immunoprecipitation with ACTH and beta-endorphin antisera, followed by acid-urea gel electrophoresis. The optimum pH for the enzyme-mediated conversion was around pH 5.0. Conversion of toad proopiocortin by NSG converting enzyme activity was inhibited by leupeptin, antipain, p-chloromercuribenzoate, and pepstatin A, but not by diisopropyl fluorophosphate, EDTA, or N-alpha-p-tosyl-L-lysine-chloromethyl ketone HCl. The results suggest that the proopiocortin-converting enzyme activity in bovine neurosecretory granules is due to an acid-thiol protease which may contain secondary hydrophobic binding sites that are involved in substrate recognition.
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PMID:Proopiocortin-converting enzyme activity in bovine neurosecretory granules. 629 Jan 88

Two anorectic drugs which stimulate serotonin neuronal activity by releasing serotonin from nerve terminals, d-fenfluramine and CM 57 277 (4-amino-[6-chloro-2-pyridyl]-1-piperidine HCl), were studied in rats. Both drugs, when given for 5 days at doses of 15 mg of d-fenfluramine per kg/day and 20 mg of CM 57 277 per kg/day, decreased body weight gain and increased content of Met5-enkephalin and beta-endorphin in hypothalamus, but not in frontal cortex or pituitary. The increase in the hypothalamic content of the two opioid peptides elicited by d-fenfluramine was reversed by metergoline and p-chlorophenylalanine, suggesting that it is mediated by serotonin. The content of two other hypothalamic neuropeptides, cholecystokinin and substance P, were not affected by d-fenfluramine. Although Met5-enkephalin content in striatum was increased transiently by d-fenfluramine, this was not a serotonin-mediated effect because it was not abolished by metergoline. The decrease in body weight gain was prevented by metergoline, but not by i.p. injection of p-chlorophenylalanine. The effect of p-chlorophenylalanine on intestine may contribute to its failure in reversing the anorectic effect of d-fenfluramine. Naltrexone, an antagonist of opiate receptor, decreased body weight gain but exerted no effect on hypothalamic Met5-enkephalin or beta-endorphin content. Taking into consideration that the increase in Met5-enkephalin and beta-endorphin may have resulted from accumulation due to decreased utilization, the anorectic effects of serotonin releasing drugs may be mediated by a reduction in the functional role of hypothalamic opioid peptides.
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PMID:Accumulation of hypothalamic endorphins after repeated injections of anorectics which release serotonin. 629 96

The effects of various test materials on plasma beta-endorphin-like immunoreactivity (beta-EpLI) were investigated in man using a specific radioimmunoassay developed by the authors. Plasma beta-EpLI was determined after extraction by the acid/acetone method (recovery 73 +/- 5%). The intraassay and interassay coefficients of variation were 5.0% and 7.6%, respectively. The plasma concentrations of human beta-EpLI in normal subjects were 11.6 +/- 4.0 pmol/l for men (n = 23) and 10.7 +/- 4.8 pmol/l for women (n = 27). Ingestion of a test meal (150 g of Campbell's condensed meat soup) resulted in a biphasic rise in plasma beta-EpLI from the basal level of 4.4 +/- 1.0 pmol/l to 29.2 +/- 1.9 pmol/l after 5 min and 24.8 +/- 6.7 pmol/l after 90 min. Intraduodenal infusion of 115 ml of 0.1 M HCl over 10 min increased the plasma beta-EpLI level from 8.7 +/- 0.5 pmol/l to 15.5 +/- 0.4 pmol/l at 10 min after the start of infusion, but the level rapidly returned to the initial value after the end of the infusion. Intramuscular injection of 4 micrograms/kg body weight of tetragastrin markedly stimulated gastric acid output and beta-EpLI release, but pretreatment with 10 mg of histamine H2 receptor antagonist inhibited the gastric acid output and plasma beta-EpLI release induced by tetragastrin. These results indicate that beta-EpLI release is stimulated by ingestion of meat soup, duodenal acidification and tetragastrin administration. It is suggested that gastric acid participates, at least in part, in postprandial release of beta-EpLI, probably from the gastrointestinal tract.
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PMID:Effect of a test meal, duodenal acidification, and tetragastrin on the plasma concentration of beta-endorphin-like immunoreactivity in man. 629 3

Both beta-endorphin and ACTH have been found in high concentrations within the hypothalami of mammals and each neuropeptide has been proposed to play a physiological role in regulating body temperature. In an attempt to determine how these peptides may alter thermoregulation, small, microgram concentrations of beta-endorphin and ACTH were injected either into lateral cerebral ventricle (ICV) or directly into the preoptic-anterior hypothalamic area (POAH) or perfused into the POAH of unrestrained rats. Core (rectal) and surface (tail) temperatures were recorded before and after ICV and POAH injection of 1 microgram of beta-endorphin or ACTH or perfusion (10 ng/microL) of either neuropeptide. POAH perfusion of naloxone HCl following the neuropeptide perfusion was tested to determine the specificity of the temperature responses. Regardless of the route of central administration, beta-endorphin, in the concentrations used, consistently evoked a hyperthermic core temperature response, that could be antagonized by naloxone. Increased core temperatures may, in part, have been due to peripheral vasoconstriction, as suggested by the decreases seen in tail temperature. The same concentrations of ACTH failed to show any prominent core temperature changes. Results suggest that beta-endorphin is a more potent modulator than ACTH in altering core temperatures of unrestrained rats. Whether beta-endorphin and ACTH act physiologically in an antagonistic manner to maintain a constant body temperature remains to be proven.
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PMID:Lateral cerebral ventricle and preoptic-anterior hypothalamic area infusion and perfusion of beta-endorphin and ACTH to unrestrained rats: core and surface temperature responses. 629 91

In order to investigate the biosynthesis of alpha MSH and beta-endorphin in a non-mammalian vertebrate, individual lizard intermediate pituitaries were incubated in complete medium containing a radioactive amino acid, using either a steady label or a pulse/chase protocol. Following incubation, acid extracts of the tissue were immunoprecipitated with either an NH2-terminal ACTH antiserum or a beta-endorphin antiserum and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. After a 24 hr steady label in medium containing [3H]tyrosine, multiple molecular weight forms of beta-endorphin-related and NH2-terminal ACTH-related radioactivity were detected. The major peak of beta-endorphin-related radioactivity co-migrated with synthetic beta-endorphin(1-31); minor peaks of beta LPH-sized material and precursor-sized material were also detected. The major peak of NH2-terminal ACTH-related material co-migrated with synthetic alpha MSH; in addition, smaller amounts of material designated ACTH biosynthetic intermediate 1, ACTH biosynthetic intermediate 2, and precursor-sized material were detected. Sequential immunoprecipitation experiments revealed that the precursor-sized material had antigenic determinants for both alpha MSH and beta-endorphin. Pulse/chase experiments established that this material is the common precursor for alpha MSH and beta-endorphin. Based on gel filtration chromatography in 6 M guanidine HCl, the molecular weights of these various peptides are: common precursor, 23,300 daltons; ACTH biosynthetic intermediate 1, 12,200 daltons; ACTH biosynthetic intermediate 2, 4,200 daltons; alpha MSH, 1,500 daltons; beta LPH, 8000 daltons; beta-endorphin, 3,400 daltons. None of the peptides precipitated with either antiserum incorporated [3H]glucosamine; thus glycosylation does not appear to be involved in this biosynthetic pathway in the lizard. The results of the kinetic experiments and molecular weight determinations indicate that the major biosynthetic pathway involves the following events: common precursor is first cleaved to yield ACTH biosynthetic intermediate 1 plus beta LPH; subsequently, beta LPH is cleaved to produce beta-endorphin; ACTH biosynthetic intermediate 1 is cleaved to produce ACTH biosynthetic intermediate 2 which is subsequently cleaved to produce alpha MSH. The pulse/chase experiments indicate minor pathways exist for cleaving beta-endorphin directly from the common precursor or via a high molecular weight form intermediate in size between the common precursor and beta LPH.
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PMID:Evidence for a common precursor for alpha MSH and beta-endorphin in the intermediate lobe of the pituitary of the reptile Anolis carolinensis. 630 Aug 8

The effect on retention of the post-training intraperitoneal administration of ACTH1-24 (0.2 or 2.0 micrograms/kg), epinephrine HCl (5.0 or 50.0 micrograms/kg), human beta-endorphin (0.1 or 1.0 microgram/kg), naloxone (0.4 mg/kg), and of the combination of naloxone or beta-endorphin with ACTH or epinephrine was studied in two different but closely related step-down inhibitory avoidance tasks in rats: task 1 (5 cm high 25 X 25 cm platform; 0.5 mA continuous footshock) and task 2 (7 X 25 cm platform, 0.3 mA discontinuous footshock). In task 1, saline control animals showed good retention in a test session carried out 24 hr later; beta-endorphin, ACTH and epinephrine caused amnesia; beta-endorphin potentiated the amnesic effect of ACTH and epinephrine; and naloxone caused memory facilitation and reversed the amnesic effect of ACTH and epinephrine. In task 2, control animals showed poor retention; beta-endorphin caused amnesia at the dose of 0.1 but not 1.0 microgram/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and beta-endorphin reversed it and transformed it into a deep amnesia. These findings suggest that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to make it amnesic. On the basis of these and previous data it seems likely that the amnesic effect of ACTH and epinephrine could be mediated by endogenous beta-endorphin release.
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PMID:Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation. 630 1


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