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)

Using the spinal superfusion procedure, in anesthetized rats and cats, the presence of active factors which displace dihydromorphine in brain opiate binding studies, has been observed. Separation of this activity on a Sephadex G-10 column reveals the presence of two fractions which occur before (Fraction I) and after (Fraction II) the salt peak which account for over 70% of the observed dihydromorphine-displacing activity. The ratio of activity in Fraction II/Fraction I is 33 and 21, in the resting spinal perfusates of the rat and cat, respectively. High intensity, bilateral stimulation of the sciatic nerve in cats, results in a 30- and 5.4-fold increase in the levels of Fraction I and Fraction II, respectively, over pre-stimulation levels. In rat, bilateral stimulation of the hind paws, resulted in a frequency-dependent increase in the levels of Fraction I (1.9- and 3.2-fold at 5 and 50 Hz, respectively). Dynorphin 1-13 fragment elutes at least partly in Fraction I. With regard to Fraction II, the peak co-chromatographs with hexapeptide derivatives of enkephalin. Met- and Leu-enkephalin (Fraction III), elute off the column at a point where opiate receptor displacing activity is relatively small. Electrophoretic separation of Fraction I radioreceptor activity of alkaline and acid pH on agarose columns revealed two principle peaks which co-migrated with alpha-neoendorphin and dynorphin 1-13. Fraction II activity appeared primarily in a single peak which was isographic with enkephalin hexapeptides. Using radioimmunoassays, detectable levels of dynorphin and Met-enkephalin were observed and sciatic nerve stimulation resulted in significant increases. Neither column-coupled radioreceptor assays nor radioimmunoassays revealed the presence of beta-endorphin. The present experiments demonstrate the releasability by high intensity somatic stimulation of a variety of opioid peptides present in spinal terminals. Significantly, however, the majority of this activity appears to be found in fractions different from those of the pentapeptide enkephalins.
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PMID:Studies on the release by somatic stimulation from rat and cat spinal cord of active materials which displace dihydromorphine in an opiate-binding assay. 686 Sep 55

The selective delta-opiate agonists D-Ser2, Leu5, Thr6-enkephalin (DSLET), D-Ala2, D-Leu5-enkephalin and D-Pen2, D-Pen5-enkephalin caused inhibition of the cholinergic contraction produced by transmural stimulation of the rat isolated jejunum. Dynorphin A, which is an agonist at both kappa- and delta-opioid receptors also inhibited the cholinergic contraction, as did leu- and met-enkephalin. The selective mu-receptor agonist D-Ala2-NMe-Phe4, Gly-ol5-enkephalin was the least potent of all peptides tested. In general, the order of potency of the peptides was similar to that reported for the delta-receptor-rich mouse vas deferens with potency values similar to those recorded previously for the hamster vas deferens. The selective delta-opioid antagonist naltrindole caused parallel shifts to the concentration-effect curve to DSLET giving a pA2 value of 10.15. The results indicate that the previously identified delta-binding sites in the rat jejunum may correspond to functional delta-opiate receptors involved in attenuating acetylcholine release.
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PMID:Evidence for functional delta-opiate receptors in the rat intestine. 769 67

The role of the endogenous opioid peptide dynorphin (1-17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin, or [D-Pen2,5]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor-binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa 2 subtype of opioid receptor. In addition, 1 microM naloxone and antisera to dynorphin (1-17) were found to increase NMDA-mediated synaptic currents. Nor-binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa 2 receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa 2 receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function.
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PMID:Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells. 791 46

Pial artery constriction following fluid percussion brain injury (FPI) is associated with elevated CSF dynorphin and beta-endorphin concentration in newborn pigs. Additionally, dynorphin is a dilator under control conditions and a vasoconstrictor under decreased cerebrovascular tone conditions. Vasopressin contributes to beta-endorphin-induced pial constriction and the constrictor potential for dynorphin. Recently, it has been observed that FPI reverses vasopressin from a dilator to a constrictor. The present study was designed to characterize the effect of FPI on beta-endorphin-induced constriction and the role of vasopressin in that constriction as well as in the reversal of dynorphin's vascular response following FPI. Brain injury of moderate severity (1.9 - 2.3 atm) was produced in anesthetized newborn pigs equipped with a closed cranial window. Dynorphin in physiologic and pharmacologic concentrations (10(-10), 10(-8), 10(-6) M) was reversed from a dilator to a constrictor following FPI (7 +/- 1, 11 +/- 1, and 16 +/- 1 vs -4 +/- 1, -7 +/- 1, and -11 +/- 1% before and after FPI, respectively). Dynorphin-induced vascular changes were accompanied by increased cortical periarachnoid CSF vasopressin and these biochemical changes were potentiated following FPI (24 +/- 4 vs 134 +/- 7 and 53 +/- 7 vs 222 +/- 14 pg/mliter for control and dynorphin (10(-6) M) before and after FPI, respectively). In contrast, in animals pretreated with the vasopressin receptor antagonist [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2-(O-methyl)-Tyr-AVP] (MEAVP, 5 micrograms/kg iv), dynorphin-induced constriction following FPI was attenuated (6 +/- 1, 12 +/- 1, and 16 +/- 1, vs -2 +/- 1, -4 +/- 1, and -7 +/- 1% before and after FPI, respectively). Additionally, beta-endorphin-induced pial constriction was potentiated following FPI (-7 +/- 1, -10 +/- 1, -15 +/- 1 vs -10 +/- 1 -15 +/- 2, and -21 +/- 2% for beta-endorphin (10(-10), 10(-8), 10(-6) M) before and after FPI, respectively). beta-endorphin-induced CSF vasopressin release was similarly potentiated following FPI. Further, MEAVP blunted the augmented constrictor responses to beta-endorphin observed following FPI (-5 +/- 1, -9 +/- 1, -14 +/- 1 vs -2 +/- 1, -5 +/- 1, and -8 +/- 1% before and after FPI, respectively). These data indicate that FPI potentiates beta-endorphin-induced pial construction and reverses dynorphin from a dilator to a constrictor. Additionally, these data show that vasopressin contributes to augmented beta-endorphin pial constriction and the reversal of dynorphin's vascular effects following FPI. Further, since CSF dynorphin and beta-endorphin concentrations are increased following FPI, these data suggest that these two opioids contribute to pial artery constriction observed following FPI, at least, in part, via the release of vasopressin.
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PMID:Role of vasopressin in altered pial artery responses to dynorphin and beta-endorphin following brain injury. 896 21

Dynorphin has long been considered the putative endogenous ligand for the kappa-opioid receptor. The high density of kappa-opioid receptors in the hypothalamus and the high concentration of dynorphin peptides in the pituitary suggest that they may play an important role in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate this possibility in early development, we examined the effects of a highly selective kappa-opioid agonist, U50488H (trans- (+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide) and dynorphin A1-13 on plasma immunoreactive adrenocorticotropin (ir-ACTH) in the ovine fetus. Although both U50488H (1.0 mg/kg i.v.) and dynorphin A1-13 (0.5 mg/kg i.v.) evoked a similar robust increase in ir-ACTH levels, the response to dynorphin A1-13 peaked at 15 min while the maximal response to U50488H was not seen until 60 min following administration. In addition, the response to dynorphin A1-13, but not U50488H, was dependent upon the gestational age of the fetus. The response to U50488H was blocked by naloxone as well as antagonists of AVP and CRF indicating that U50488H is eliciting its effects via opioid receptors, most likely of the kappa receptor subtype, at the hypothalamus. Conversely, the dynorphin A1-13 response was not blocked by any of the aforementioned antagonist. Thus, it appears that dynorphin A1-13 may act as a direct mediator of ACTH release via nonopioid receptors at the level of the pituitary.
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PMID:Differential mechanisms of ovine fetal pituitary stimulation by a selective kappa-opioid agonist and by dynorphin. 899 74

We previously reported that U50488H, a kappa-selective opioid agonist, stimulates the release of adrenocorticotropin (ACTH) in the ovine fetus via the release of hypothalamic arginine vasopressin and corticotropin releasing factor. In this study we examined the effects of the endogenous kappa-preferring opioid peptide, dynorphin A1-13, on fetal ACTH release using the unanesthetized, chronically catheterized fetal lamb model. Fetal plasma samples were collected at timed intervals after fetal administration of dynorphin A1-13 (0.5 mg/kg, i.v.) and subsequently analyzed by radioimmunoassay for immunoreactive-ACTH and immunoreactive-cortisol. Dynorphin A1-13 produced a highly significant and rapid increase in immunoreactive-ACTH (P = .002) and immunoreactive-cortisol (P = .002) with peak levels of 383.3 +/- 43.8 pg/ml and 32.8 +/- 9.0 ng/ml, respectively, at 15 min after administration. A similar increase in plasma immunoreactive-ACTH was seen after the same dose of dynorphin A1-17 (P = .02) but not dynorphin A2-17. This ACTH response to dynorphin A1-13 was shown to be insensitive to the opioid antagonist, naloxone (12 mg/hr), as well as antagonists of corticotropin releasing factor and arginine vasopressin. These data suggest that dynorphin A1-13 in the ovine fetus may be acting through a mechanism distinct from the kappa-opioid system and that the dynorphins may serve as secretagogues of ACTH directly at the anterior pituitary through nonopioid receptors.
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PMID:Dynorphin A1-13 stimulates ovine fetal pituitary-adrenal function through a novel nonopioid mechanism. 899 23

Dynorphins and beta-endorphin in human plasma were characterized and studied quantitatively using radioimmunoassay, high-performance liquid chromatography (HPLC), and mass spectrometry. Most immunoreactive (ir) dynorphin B and beta-endorphin in human plasma coeluted with authentic peptides in analysis. Dynorphin A was not detected. Added to human plasma it was rapidly converted into Leu-enkephalin-Arg6 followed by elimination of the C-terminal arginine after prolonged incubation. The rate of dynorphin A conversion was estimated at 40 pmol/min/microl plasma. This process was inhibited by the thiol protease inhibitor, PHMB and by EDTA. Dynorphin B, alpha-neoendorphin and big dynorphin were virtually not metabolized by plasma proteases under the same conditions. beta-endorphin was processed into beta-endorphin(1-19) and the corresponding C-terminal counterpart beta-endorphin(20-31) at a rate of about 25 pmol/min/microl of plasma. Based on the above data, a reliable strategy was established to measure dynorphin B- and beta-endorphin-ir in human plasma samples. The basal levels in a male control group were 0.99 +/- 0.11 (n = 11) and 16.3 +/- 1.5 (n = 11) fmol/ml plasma, respectively.
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PMID:Characterization of immunoreactive dynorphin B and beta-endorphin in human plasma. 980 46

It has been well known that immune function is modulated by endogenous opioid peptides: beta-endorphin and enkephalins. However, the effect of dynorphin A on the immune function has not been well documented. In this study, we investigated dynorphin A in the regulation of mitogen-induced proliferation and and interleukin-2 (IL-2) production of rat splenocytes. The results showed that dynorphin A 1-13 as well as dynorphin A 1-17 enhanced concanavalin A-stimulated [(3)H] thymidine uptake 46-112% and IL-2 production in a dose-dependent fashion. These effects were reversed by naloxone and norBNI, a selective kappa-receptor antagonist. Dynorphin A reduced cyclic AMP contents in spenocytes in naloxone and norBNI reversible fashion. The data suggest that dynorphin A enhanced mitogen-stumulated lymphocyte proliferation and IL-2 production via kappa-opioid receptor and cAMP pathway.
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PMID:Dynorphin A enhances mitogen-induced proliferative response and interleukin-2 production of rat splenocytes. 1065 83

Dynorphin (Dyn) peptides were previously shown to increase plasma corticotropin (ACTH) in the ovine fetus, but the site of its action remains unclear. In the present study, Dyn A(1-17) was found to stimulate ACTH release from mouse anterior pituitary tumor AtT-20 cells in a dose-dependent manner. Naloxone did not block the effect of Dyn A(1-17) and the selective kappa-opioid receptor agonist U50488H did not stimulate ACTH release. Dyn A(2-17), a degradative peptide fragment that does not bind to opioid receptors, also stimulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) receptors, the ACTH-releasing effects of Dyn A(1-17) in AtT-20 cells were not affected by co-administration of NMDA receptor antagonist LY235959. The ACTH response to Dyn A(1-17) could not be blocked by alpha-helical CRH (CRH antagonist) and was additive with a maximal stimulatory dose of CRH, suggesting different mechanisms of action. These results show that the release of ACTH by Dyn A(1-17) in AtT-20 cells is not mediated by kappa-opioid receptors or by the NMDA receptor.
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PMID:Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms. 1072 88

We have previously shown that beta-endorphin (END) is contained and released from memory-type T-cells within inflamed tissue and that it is capable to control pain (J Clin Invest 100(1) (1997) 142). Methionine-enkephalin (MET) and Dynorphin-A (DYN) are endogenous opioids with preference for delta- and kappa-opioid receptors, respectively. Both MET and DYN are produced and contained within immune cells. The goal of this study was to determine the release characteristics of MET and DYN in a rat model of localized hindpaw inflammation and to examine the antinociceptive role of MET and DYN in a Freund's adjuvant induced model of inflammatory pain. We found that corticotropin-releasing factor (CRF) can stimulate the release of both MET and DYN from lymphocytes. This release is dose-dependent and reversible by the selective CRF antagonist alpha-helical-CRF. Furthermore, CRF (1.5 ng) produces analgesia when injected into the inflamed paw, which is reversible by direct co-administration of antibodies to MET. Lymphocyte content of MET was 7.0+/-1.4 ng/million cells, whilst DYN content was ~30-fold lower. Both END and DYN, but not MET, were released by IL-1. Consistently, IL-1 produced peripheral analgesic effects which were not reversed by antibodies to MET. These results indicate that both MET and DYN play a role in peripheral analgesia but have different characteristics of release. These studies further support a role of the immune system in the control of inflammatory pain. This may be particularly important in patients suffering from compromised immune systems as with cancer and AIDS.
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PMID:Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain. 1151 79


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