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)

In vitro competition studies with rat brain were performed to systematically define the characteristics of the [3H]U-69,593 binding site and of the site selectively labeled by [3H]EKC (in the presence of U-69,593 and mu and delta blocking agents). The [3H]U-69,593 site has a binding selectivity profile that corresponds to that of the kappa opiate receptor. That is, all kappa compounds, regardless of chemical class, and dynorphin A, the putative endogenous ligand for kappa receptors, bind to the site with high affinities, whereas mu and delta ligands and nonopiate compounds do not. The agonists U-69,593, ICI 197,067 and U-50,488 and antagonist nor-binaltorphimine were found to have a useful degree of selectivity for the site. The [3H]EKC site has opiate receptor characteristics and appears to be the most abundant opiate receptor in rat brain, but its binding selectivity profile is not that of a kappa receptor. Instead, this non-mu, non-delta, non-kappa site has the pharmacological properties that correspond to those of the beta-endorphin-specific, epsilon receptor that has been hypothesized to exist for some time. We could not identify any compound that is selective for the putative epsilon site. Of the more than 50 compounds tested, all were either equally potent at the [3H]U-69,593 and [3H]EKC sites or were more potent at the [3H]U-69,593 site.
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PMID:Affinity of drugs and peptides for U-69,593-sensitive and -insensitive kappa opiate binding sites: the U-69,593-insensitive site appears to be the beta endorphin-specific epsilon receptor. 216 90

Interleukin 1 (IL1) is a macrophage-derived polypeptide which signals neurons in the preoptic-anterior hypothalamus to initiate fever and the acute-phase glycoprotein response. Recently, increases in cerebrospinal fluid and hypothalamic levels of beta-endorphin have been reported during endotoxin (LPS)- and IL1-induced fevers, suggesting that this opioid may participate in the modulation of IL1 effects in the CNS. In this study, we investigated whether purified (human) IL1 influences the specific binding of three prototypic opioid agonists (2-D-alanine-5-L-methionineamide, DAME; (-)-ethylketocyclazocine, EKC; dihydromorphine, DHM) and one antagonist (naloxone) to opioid receptor-enriched membrane preparations in cerebral cortex, hypothalamus, midbrain, pons, medulla, and cerebellum of guinea pig brain. IL1 reduced the binding of these ligands to their receptors during a 30-min incubation. The extent of IL1 inhibition of a given ligand for its binding sites varied according to the brain region; within some regions, the extent of this inhibition also varied with the four ligands tested. But in cortex the effect of IL1 on the specific binding of DHM is dose-dependent. Similar results were obtained with crude homologous IL1. S. enteritidis endotoxin, suspended in pyrogen-free saline at concentrations from 4 to 36 micrograms/ml, did not inhibit the binding of these opioid ligands to their receptors in any brain region. These results indicate that IL1 interacts with the opiate receptors in guinea pig brain. This interaction, moreover, is not limited to the hypothalamus alone, the primary site of the pyrogenic action of IL1, but also occurs in other brain regions.
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PMID:Interleukin 1 reduces opioid binding in guinea pig brain. 301 Feb 57

The role of endogenous opioid systems (endogenous opioids and opioid receptors) in human cancer was explored using an opioid antagonist paradigm and neuroblastoma cells (SK-N-MC) transplanted into nude mice. Mice inoculated with 2.5 X 10(6) neuroblastoma cells received daily injections of either 0.1 or 10 mg/kg naltrexone (=0.1 and 10 NTX groups) which blocked the opioid receptor for 6-8 hr/day or the entire 24 hr/day, respectively, or sterile water. The latency for appearance of a measurable tumor (5 mm diameter) in the 0.1 NTX group was 27% longer than controls (11 days), and the first death in this group occurred 33% later than controls (day 27). Mice inoculated with tumor cells in the 10 NTX group had an acceleration (18%) in the latency of tumor appearance and, 2 weeks after cell inoculation, 70% of the mice in this group had tumors, in contrast to 10% of the controls. At the termination of the experiment (day 45), only 33% of the 10 NTX group were alive, in contrast to 90% of the controls. Receptor binding assays using DAGO, DADLE, or EKC revealed specific saturable binding only for DADLE and EKC. NTX administration resulted in a 148-186% increase in density for both binding sites, but no changes in binding affinity. Measures of opioid levels showed that tumor tissue levels of both beta-endorphin and methionine-enkephalin were elevated 2.5 to 6.5 fold from control values in both NTX groups, whereas plasma beta-endorphin was subnormal by 4 to 6 fold. These results indicate that endogenous opioid systems regulate human neuro-oncogenesis, with opioids being active inhibitors of growth. Opioid antagonists up-regulate receptors and increase tissue levels of endogenous opioids and, under conditions in which the opioid antagonist is short-acting (e.g., 0.1 NTX), can have an exaggerated antitumor effect during the interval when the antagonist is no longer present.
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PMID:Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems. 304 Nov 43

Using prototypic ligands for each type of opioid receptors (mu, delta, kappa, and sigma) as well as compounds derived from each class of endogenous opioid peptides (beta-endorphin, enkephalins, and dynorphins), we have undertaken the characterization of adrenomedullary opioid binding sites. The specific binding of [3H]etorphine ([3H]ET) to a membrane preparation of bovine adrenal medulla was greatly increased when the incubation temperature was raised from 22 to 37 degrees C. Characterization of the opioid binding sites was obtained at 37 degrees C with [3H]ET (nonspecific opioid ligand), [3H]ethylketocyclazocine ([3H]EKC; kappa), [3H]dihydromorphine ([3H]DHM; mu), [3H]-[D-Ala2,D-Leu5]enkephalin ([3H]DADLE: delta), and N-[3H]allylnormetazocine ([3H]SKF-10047; sigma) in the absence or presence of blocking agents for cross-reacting receptors. [3H]ET had a high affinity binding site (KD = 0.98 nM) with a Bmax of 119 pmol/g protein. All the other opioid compounds showed biphasic saturation curves with KD ranging from 0.6 to 1.29 nM for the high affinity binding site and from 2.49 to 12.1 nM for the low affinity binding site. The opioid mu-receptor was characterized by the high affinity binding site for [3H]DHM (KD = 1.29 nM; Bmax = 38 pmol/g protein). Blockade of the cross-reacting receptor sites for [3H]EKC, [3H]DADLE, and [3H]SKF-10047 revealed the presence of kappa (KD = 0.66 nM; Bmax = 12 pmol/g protein), kappa 2 (benzomorphan site; KD = 11.1 nM; Bmax = 56 pmol/g protein), delta (KD = 0.67 nM; Bmax = 4.7 pmol/g protein), and sigma (KD = 4.54 nM; Bmax = 32 pmol/g protein) opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Opioid receptors in bovine adrenal medulla. 609 79

Opiate kappa agonists were administered into the cisterna magna of normotensive urethane-anaesthetized artificially ventilated rats: ethylketocyclazocine (78.7 nM) (EKC) and dynorphin-(1-13) (62.3 nM) produced significant and long-lasting decreases in both blood pressure and heart rate. High doses of naloxone (1 mg/kg i.v.) were required to partially antagonize these effects. The central cardiovascular effects of EKC and dynorphin-(1-13) were compared to those of fentanyl (3 nM), [D-Ala2,Met5]enkephalinamide (17 nM) and beta-endorphin (2.9 nM) which induced increases in blood pressure and heart rate. These results suggest that opposite central cardiovascular effects could be induced by activation of various opiate receptors.
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PMID:Central cardiovascular effects of kappa agonists dynorphin-(1-13) and ethylketocyclazocine in the anaesthetized rat. 631 58