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)

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.
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PMID:Possible action of human placental aminopeptidase N in feto-placental unit. 790 13

The analgesic property of the anesthetic gas N2O has long been known and used to treat pain in clinical medicine and dentistry. The present study was conducted to identify by subtype and possible location the brain opioid receptors that mediate N2O antinociception in rats. A 5-min exposure to 70% N2O consistently evoked an antinociceptive effect in the hot plate test. This drug effect was partly antagonized in dose-related fashion by i.c.v. pretreatment with naltrexone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and beta-endorphin, which block multiple, mu and epsilon opioid receptors, respectively. However, the N2O-evoked antinociception was unaffected by i.c.v. pretreatment with either the delta opioid antagonist naltrindole or the kappa opioid antagonist nor-binaltorphimine. When D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 was administered intracerebrally directly into the periaqueductal gray, N2O antinociception was partly antagonized in a dose-dependent manner. The antinociceptive response to N2O was uninfluenced by beta-endorphin administered into the periaqueductal gray. The findings of these pharmacological antagonism studies are consistent with the hypothesis that exposure to N2O causes a neuronal release of beta-endorphin. These results indicate that supraspinal mu and epsilon opioid receptors mediate N2O antinociception in the rat hot plate paradigm and that one central site of such mu but not epsilon opioid receptors is the periaqueductal gray.
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PMID:Antagonism of nitrous oxide antinociception in the rat hot plate test by site-specific mu and epsilon opioid receptor blockade. 818 25

Receptors mediating opiate-induced inhibition of potassium-stimulated release of [3H]norepinephrine (NE) from slices of rat cortex incubated in vitro have been characterized by comparison of the pA2 values of the competitive antagonists, naloxone, D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine, naltrindole and bremazocine against the agonists, Tyr-D-Ala-MePhe-Gly-ol (DAMGO), Tyr-D-Arg-Phe-Sar (TAPS), [D-Ser2, Leu5]enkephalyl-Thr (DSLET), beta-endorphin [beta-END(1-31)] and ethylketocyclazocine (EKC). There were significant differences among agonists in their sensitivities to each antagonist. The delta receptor selective agonist, DPDPE, and the kappa 1-agonist, U69593, did not inhibit NE release, indicating that delta and kappa 1 receptors are not involved. DAMGO, TAPS and DSLET generally behaved as mu agonists, although TAPS and DSLET were less sensitive to antagonism by CTOP than by DAMGO. TAPS and DSLET showed similar sensitivities to all antagonists, suggesting that they acted through similar receptors, possibly of the mu 1 type. beta-END(1-31) and EKC differed from DAMGO and from each other in their sensitivities to most antagonists. Shifts in agonist concentration-response curves induced by prior treatment of the rats with the noncompetitive antagonists, beta-funaltrexamine and naloxonazine, also suggested that EKC and beta-END(1-31) acted through mechanisms differing from those used by DAMGO, TAPS and DSLET. It is possible that EKC and beta-END(1-31) acted via kappa 2 and/or epsilon receptors. These results suggest that there is heterogeneity in the opioid receptors regulating NE release in rat cortex.
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PMID:Inhibition of norepinephrine release from rat cortex slices by opioids: differences among agonists in sensitivities to antagonists suggest receptor heterogeneity. 826 76

It has been shown previously that opioids induce antinociceptive effects at peripheral sites in the presence of inflammatory processes. Besides being elicited by local injection of opioids, such effects can also be obtained by activation of intrinsic opioid mechanisms, e.g. following stress. In the present study the possible role of cytokines in this mechanism was investigated. Unilateral inflammation of the hindpaw of rats was induced by local injection of Freund's complete adjuvant. Intraplantar injection of tumor necrosis factor alpha (TNF alpha) or interleukin-6 induced a dose-dependent increase in the threshold in the paw pressure test in the inflamed but not in the non-inflamed paw. This increase was prevented by local injection of naloxone and the mu-opioid receptor specific antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) as well as by 3-E7, an universal opioid peptide antibody. In rats pretreated with cyclosporin A to suppress the immune system, the antinociceptive effect of TNF alpha was completely inhibited. In concert with previous studies these data indicate that the tested cytokines release opioid peptides (e.g. beta-endorphin and/or enkephalins) from immune cells of the inflamed tissue which act on opioid receptors present on sensory nerve terminals, resulting in antinociception.
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PMID:Peripheral mechanisms of opioid antinociception in inflammation: involvement of cytokines. 828 87

Thymidine incorporation into DNA was inhibited dose-dependently by beta-endorphin in rat fetal brain cell aggregate cultures. The inhibition was reversed partially by mu (cyclic D-Phe-Cys-Tyr-D-Trp-Orn-Thr- Pen-Thr amide) or kappa (norbinaltorphimine) antagonists. Complete blockade of the beta-endorphin inhibitory effect was achieved only on concomitant exposure to both antagonists. Eadie-Hofstee analysis revealed that beta-endorphin inhibited thymidine incorporation noncompetitively. In the presence of protease inhibitors, beta-endorphin decreased thymidine incorporation with an IC50 of 0.7 nM. Truncated and N-acetylated beta-endorphin derivatives, which bind with low affinity to opioid receptors, did not affect thymidine incorporation. These findings indicate that beta-endorphin at physiological concentrations can regulate thymidine incorporation in cultured brain cells.
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PMID:Beta-endorphin is a potent inhibitor of thymidine incorporation into DNA via mu- and kappa-opioid receptors in fetal rat brain cell aggregates in culture. 838 Apr 43

The carboxyl-terminal tripeptide of alpha-MSH(1-13), Lys-Pro-Val, antagonizes anorexia induced by interleukin-1 beta (IL-1). The present studies were undertaken to determine if the Lys-Pro dipeptide portion of this tripeptide likewise antagonizes anorexia induced by ICV administration of 0.5 pmol IL-1 in rats previously deprived of food. This dose of Lys-Pro did significantly attenuate the IL-1-induced anorexia, but only for 1 h after infusion. Simultaneous administration of a larger dose (5.0 pmol) of Lys-Pro reversed the IL-1-induced anorexia during both the 0-1-h and 2-4-h periods. In addition, both 0.5 and 5.0 pmol of the D-substitute tripeptide, Lys-D-Pro-Thr (LDPT), similarly attenuated the IL-1-induced anorexia. The ICV administration of 5.0 pmol Lys-Pro also did not have any significant effects on food consumption. These results indicate that the dipeptide Lys-Pro may have a short-term antagonistic action against the anorexia induced by IL-1, and it is possible that this action may be partially mediated by the blockade of IL-1 on its own receptor.
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PMID:The dipeptide Lys-Pro attenuates interleukin-1 beta-induced anorexia. 838 84

Using reversed-phase HPLC in combination with a radioimmunoassay for ovine corticotropin-releasing hormone (CRH), a peptide with CRH-like immunoreactivity was isolated in pure form from an extract of the caudal spinal cord region of the spotted dogfish, Scyliorhinus canicula. The primary structure of the peptide was established as Pro-Ala-Glu-Thr-Pro-Asn-Ser-Leu10-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg- Glu-Met-Ile- Glu20-Ile-Ala-Lys-His-Glu-Asn-Gln-Gln-Met-Gln30-Ala-Asp-Ser- Asn-Arg-Arg-Ile-Met - Asp-Thr40-Ile.NH2. This amino acid sequence shows moderate structural similarity to Catostomus urotensin I (51%) and to human CRH (56%). The data provide, therefore, chemical evidence to support the conclusions of earlier immunohistochemical studies that the diffuse caudal neurosecretory system of elasmobranchs produces a peptide that is immunochemically related to teleost urotensin I peptides. However, the primary structure of urotensin I has been poorly conserved during evolution.
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PMID:A peptide from the caudal neurosecretory system of the dogfish Scyliorhinus canicula that is structurally related to urotensin I. 853 45

Our laboratory has previously shown that intracerebroventricular (i.c.v.) administration of beta-endorphin suppresses brain and liver ornithine decarboxylase activity (ODC; a growth regulatory enzyme) in preweanling rats. This investigation examined, in 6-day-old rats, the relative participation of brain mu-, delta- and epsilon-opioid receptors in beta-endorphin's ODC effects, by comparing tissue ODC responses to beta-endorphin given alone i.c.v. and in the presence of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-opioid receptor antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; delta-opioid receptor antagonist) or beta-endorphin-(1-27) (epsilon-opioid receptor antagonist). Administration of 0.5 microgram of beta-endorphin alone significantly decreased brain and liver ODC activity 4 h after injection, and the effect was completely blocked by coinjection of CTOP (0.075 micrograms) but not by ICI-174,864 (0.75 or 3.75 micrograms) or beta-endorphin-(1-27) (3.75 or 7.5 micrograms). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 microgram) or ICI-174,864 alone was accompanied by increased levels of basal ODC activity. The results obtained demonstrate that i.c.v. beta-endorphin downregulates ODC expression in central as well as in peripheral tissues by interacting with brain mu-opioid receptors, but not with delta- or epsilon-opioid receptors or mu/delta-opioid receptor complexes. Also, they indicate that endogenous opioid systems have a tonic inhibitory influence on ODC activity which is mediated, at least in part, by mu- and delta-opioid receptors.
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PMID:The inhibition of ornithine decarboxylase activity in developing rat tissues by central nervous system beta-endorphin is mediated by mu-opioid receptors, but not by delta- or epsilon-opioid receptors. 854 35

Based on the differential abilities of the opioid antagonists naltrexone and D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) to antagonize the antinociceptive action of beta-endorphin and morphine in the rat periaqueducatal gray (PAG), three pharmacologically distinct mechanisms were determined to mediate the antinociceptive effect of beta-endorphin. Two of these mechanisms are unique to beta-endorphin, possess a high affinity for CTP and can be discriminated based on their differential sensitivity to naltrexone. The third mechanism displays characteristics common to that activated by morphine. The results of radioligand binding studies were consistent with these observations. [125I]-beta-Endorphin labeled a population of sites in the PAG which (compared to those labeled by [3H]morphine) displayed a significantly higher affinity for CTP. In addition, a naltrexone-insensitive binding component was identified in the [125I]-beta-endorphin, but not [3H]morphine assays. Furthermore, comparable competitor affinities were determined across assays, suggesting an interaction of the radioligands with common PAG sites. A naltrexone-insensitive component to beta-endorphin antinociception also was identified in studies which evaluated the ability of the antagonist to shift the beta-endorphin dose-response curve. Interestingly, the ability of low doses of CTP and naltrexone to inhibit increasing doses of beta-endorphin was described by a U-shaped dose effect curve. The response to low and high, but not intermediate, doses of beta-endorphin were antagonized by picomole doses of both antagonists. As there was no evidence for allosteric interactions between [125I]-beta-endorphin binding sites in the PAG, it appears that beta-endorphin also may activate pain facilitory mechanisms which counterbalance its overall antinociceptive effect.
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PMID:Biochemical and pharmacological characterization of multiple beta-endorphinergic antinociceptive systems in the rat periaqueductal gray. 855 58

Products formed during cyanogen bromide (CNBr) digestion of alpha-endorphin, beta-endorphin, and horse heart myoglobin are examined using reversed-phase high-performance liquid chromatography and electrospray mass spectrometry. It is demonstrated that unstable intermediate reaction products may be formed, as well as oxidized products when the CNBr reaction is performed in 0.1% TFA in water/acetonitrile (6:4 v/v) and that, under other conditions commonly employed for the CNBr cleavage reaction, unstable intermediate products are also generated. The formation of the expected cleavage products is found to be improved by adjusting the hydrolysis conditions. The structure of the intermediate formed from alpha-endorphin is examined using electrospray mass spectrometry in combination with low-energy collision-induced dissociation and tandem mass spectrometry and is shown to have a cyclic hydrated homoserine iminolactone part. The results obtained in this study explain the formation of partially cleaved proteins in the case of Met-Thr-containing sequences, which likely have a cyclic hydrated homoserine iminolactone part instead of the putative homoserine residue.
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PMID:Characterization of unstable intermediates and oxidized products formed during cyanogen bromide cleavage of peptides and proteins by electrospray mass spectrometry. 884 40


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