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)

Evidence is provided for the abilities of endogenous 6-(Arg or Lys)-opioid peptides to interact with kappa-receptors as agonists. Dynorphin-(1-17) and -(1-8), alpha- and beta-neo-endorphin, [Met5]-enkephalin-Arg6-Phe7 and des acetyl salmon endorphin I significantly inhibited the electrically-evoked contractions of rabbit vas deferens which had been shown to contain kappa-receptors exclusively, indicating that endogenous 6-(Arg or Lys)-opioid peptides could act on kappa-receptors as agonists. Additionally, the inhibition of contractions of rabbit vas deferens by 6-(Arg or Lys)-opioid peptides was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors. This also suggested that 6-(Arg or Lys)-opioid peptides acted as kappa-receptor agonists. The rank order of the inhibitory potency of 6-(Arg or Lys)-opioid peptides against contractions of rabbit vas deferens was as follows: dynorphin-(1-17) greater than alpha-neo-endorphin greater than beta-neo-endorphin .=. dynorphin-(1-8) greater than des acetyl salmon endorphin I greater than [Met5]-enkephalin-Arg6-Phe7. Since other endogenous opioid peptides such as [Met5]- and [Leu5]-enkephalin and beta-endorphin have been shown not to act on kappa-receptors as agonist, data in the present study suggest that endogenous opioid peptides can be classified into two groups in terms of an ability to interact with kappa-receptors as an agonist.
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PMID:Evidence that endogenous 6-(ARG or LYS)-opioid peptides can interact with kappa-receptors as agonists. 613 Apr 30

Dynorphin(1-8) immunoreactivity was visualized by immunohistofluorescence in hypothalamic magnocellular neurons of the rat. No immunoreactive met-enkephalin-Arg6-Gly7-Leu8, a fragment of the adrenal medulla pro-enkephalin molecule, was detected in magnocellular neurons. However, a strong met-enkephalin-Arg6-Gly7-Leu8-like immunostaining was seen in other regions of the brain. These results suggest that in magnocellular neurons dynorphin(1-8) exists independently from pro-enkephalin and therefore the magnocellular neurons represent a third opioid peptide neuronal system in brain. These observations, however, do not rule out a coexistence of proenkephalin and dynorphin-related peptides in other regions of the brain.
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PMID:Immunohistochemical localization of dynorphin (1-8) in hypothalamic magnocellular neurons: evidence for absence of proenkephalin. 613 Apr 34

Nanomolar concentrations of neurotensin caused a dose-dependent contraction of the longitudinal muscle layer of the guinea-pig ileum. The contractile activity of neurotensin was partially blocked by tetrodotoxin or atropine, indicating that a component of the neurotensin-mediated contraction is indirect in nature and likely involves the release of endogenous acetylcholine from nervous terminals in the myenteric plexus. Dynorphin and related peptide fragments also blocked in part the neurotensin contraction; the potency of this opioid peptide was about the same as that of atropine. Other peptides and alkaloids tested for ability to block the neurotensin contractures included the enkephalins, beta-endorphin, normorphine and the ketocyclazocines; all these opioids inhibited in a dose-dependent fashion the neuronal component of the excitatory effect of neurotensin. The potency of these compounds to reduce the contractions of neurotensin showed good correlation with the potency of these agents to depress by 50% the electrically evoked neuromuscular twitches in the same tissue (r = 0.99); in these tests dynorphin was found to be the most potent of the endogenous opioid-like peptides. The dynorphin blockade was selective to the excitatory effect of neurotensin because the opioid peptide did not antagonize the contractile action of acetylcholine, histamine, substance P, angiotensin II, bradykinin, Ba++ or K+ ions. In addition, somatostatin, vasointestinal peptide, gastrin or adenosine did not modify the potency of neurotensin whereas thyrotropin releasing hormone and epinephrine caused a modest doubling of the neurotensin EC50. The inhibitory action of dynorphin was reduced in the presence of naloxone, suggesting that the interaction involved opiate receptors. Morphine tolerance was not extended to the inhibitory action of dynorphin as evidenced by the finding that the potency of dynorphin-(1-13) to block the neurotensin responses was increased after chronic morphine exposure. In contrast, the potency of dynorphin-(1-13) was significantly reduced in tissues rendered tolerant to the action of ketocyclazocine or ethylketocyclazocine, suggesting that the action of dynorphin could be partially mediated via occupation of K-opiate receptors. Thus, a cholinergic-neuronal component activated by neurotensin on the myenteric plexus appears to be under the inhibitory influence of opiate receptors, suggesting that dynorphin may play a role in the modulation of cholinergic synapses on the enteric nervous system.
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PMID:Dynorphin inhibition of the neurotensin contractile activity on the myenteric plexus. 614 Dec 81

Previous studies have shown that morphiceptin is a highly selective mu-receptor agonist. Recently we have obtained a more potent and stable analog, Tyr-Pro-NMePhe-D-Pro-NH2 (PL017). This peptide retains mu-receptor selectivity. beta-Endorphin is known to be a potent but non-selective opioid peptide for mu-, delta- and benzomorphan binding sites. Dynorphin is a putative kappa-agonist with significant affinity to mu-, delta- and benzomorphan binding sites in rat brain membranes. To understand the structural requirement for receptor type selectivity the enkephalin sequence of beta-endorphin and dynorphin was replaced by that of morphiceptin analog. Replacing the Met-enkephalin sequence of beta h-endorphin by PL017 yields a peptide highly selective for mu-binding sites. Substituting the Leu-enkephalin sequence of dynorphin-17 produces a peptide [PL017-dynorphin(6-17)] that retains high affinities for mu- and kappa-binding sites and has very low affinities for delta- and benzomorphan binding sites. These results suggest that a morphiceptin sequence at the amino-terminus of large opioid peptides can dictate mu-receptor selectivity. An enkephalin sequence at the amino-terminus of large opioid peptides seems to be required to retain high affinity for delta- and benzomorphan binding sites. The high affinity of PL017-dynorphin(6-17) for kappa-binding sites but not for benzomorphan binding sites suggests that benzomorphan sites of rat brain are not kappa-sites.
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PMID:The role of amino-terminal sequence of beta-endorphin and dynorphin in the determination of opiate receptor type selectivity. 614 89

Dynorphin (1-17), and to a lesser extent, beta-endorphin and [Leu]enkephalin (10(-6) M each) decreased the spontaneous release of vasopressin (VP) from the rat neurointermediate pituitary in vitro, whereas the oxytocin (OT) release remained unchanged. Naloxone, however, did not significantly alter the spontaneous VP and OT release. Dynorphin (1-17) (10(-7) M) increased the electrically evoked release of VP and OT, while 10(-6) M had a significant, somewhat less pronounced stimulatory effect only on VP, but not on OT release. The opiate inactive fragment [des-Tyr1]dynorphin (1-17) did not change the evoked VP and OT release, indicating that the dynorphin effect was mediated by opiate receptors. beta-Endorphin (10(-6) M and 10(-7) M) did not alter the evoked VP and OT secretion. 10(-6) M [Leu]enkephalin induced a stimulation of the evoked OT, but not VP release; 10(-7) M [Leu]enkephalin had no effect, neither on VP nor on OT release. The opiate antagonist naloxone (10(-5) M) induced an increase in the evoked VP and, even more pronounced, OT release. In a concentration of 10(-6) M, however, naloxone only increased the evoked OT release. When naloxone and dynorphin (1-17) were concomitantly applied, their stimulatory effects on the evoked VP and OT release were additive. Similarly to the effects of naloxone, addition of a monoclonal antibody which binds to the common N-terminal sequence of all endogenous opioid peptides, resulted in a marked increase in the evoked secretion of VP and, to an even more pronounced degree, of OT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of various opioid peptides on vasopressin and oxytocin release from the rat pituitary in vitro. 615 15

The histamine-releasing effect of certain opiate drugs prompted a survey of endogenous opiates for mast cell-secretagogue activity. Since intestinal mucosal mast cells (MMC) differ from connective tissue mast cells in their response to a variety of secretagogues and anti-allergic compounds, we have examined the influence of several endogenous opiate peptides on histamine secretion from the two mast cell types in the rat. MMC hyperplasia was induced in rats infected with the nematode Nippostrongylus brasiliensis and MMC were isolated by collagenase digestion from the small intestine. Connective tissue mast cells from the peritoneal cavity (PMC) were isolated by peritoneal lavage. Dynorphin, alpha-neoendorphin, and beta-endorphin had a concentration-dependent secretagogue effect (10(-6)M to 10(-4)M) on PMC that was temperature and energy dependent, but MMC from the same animals were unresponsive to these agents. Differences between PMC and MMC did not appear to be attributable to the MMC isolation procedure since PMC treated similarly remained responsive to endorphin. Endorphin-induced histamine secretion from PMC was partially inhibited by the anti-allergic agent disodium cromoglycate. Inhibition with the opiate antagonist naloxone was nonspecific, occurring only at concentrations that also inhibited antigen-induced mediator release. Mast cell secretion induced by certain opiate peptides may therefore be nonreceptor mediated and relate to a direct membrane effect by basic peptides.
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PMID:The influence of endorphins on peritoneal and mucosal mast cell secretion. 620 30

Pretreatment of mice with a single injection of morphine, beta-endorphin, Leu-enkephalin, FK33824 or [D-Ala2-D-Leu5]enkephalin, for 3 h increased the ability of naloxone to antagonize the analgesic effects of morphine. However, dynorphin-(1-13) can only antagonize morphine, beta-endorphin or Leu-enkephalin induced increased naloxone efficacy but not FK33824 or [D-Ala2-D-Leu2]enkephalin. Dynorphin itself can also increase naloxone efficacy when treated alone. However, this effect can be prevented when animals are pretreated with dynorphin and naloxone together.
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PMID:Possible regulatory role of dynorphin-(1-13) on narcotic-induced changes in naloxone efficacy. 627 44

Intracerebroventricular administration of 20, 40 and 60 nmol of dynorphin (1-13) produced analgesia, as assessed by flinch/jump response to footshock, and hypothermia in the rat. Rats developed tolerance to both the analgesic and thermic effects of the 20 nmol dose of dynorphin. Dynorphin and beta-endorphin showed cross-tolerance with respect to their analgesic but not their thermic effects. Dynorphin and morphine also produced cross-tolerant analgesic effects. Naloxone (10 mg/kg, IP) completely blocked the barrel rolling produced by 20 nmol dynorphin but did not alter its analgesic or thermic effects.
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PMID:Dynorphin (1-13): analgesia, hypothermia, cross-tolerance with morphine and beta-endorphin. 628 45

The demonstration of the immunoreactive proopiomelanocortin (POMC) peptides beta-endorphin (beta-E), beta-lipotropin (beta-LPH), alpha-melanotropin (alpha-MSH), and corticotropin (ACTH) in the human placenta or in tissue cultures of placental origin using radioimmuno-, bio-, or radioreceptor assay suggested that opioid peptide hormones or their precursors are synthesized in the placenta. In order to test this hypothesis, we tried to localize opioid peptides immunohistochemically. On neighbouring sections of the placenta which were incubated with antisera against beta-E, beta-LPH, alpha-MSH, ACTH, BAM-12 P, BAM-22 P, Heptapeptide, alpha-Neoendorphin and Dynorphin 1-17, the immunoperoxidase method was used. The placenta and the pituitary of perfusion-fixed rats were used for controls. The negative immunohistochemical findings in the human and rat placenta do not support the view that beta-E, beta-LPH, alpha-MSH and ACTH are synthesized in the syncytiotrophoblast of this organ. The site of origin of proopiomelanocortin peptides which are present in the maternal and the fetal plasma most likely is the maternal and fetal pituitary.
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PMID:Immunohistochemical studies on opioid peptides in the human placenta. 631 29

The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that beta-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its "anti-endorphin" actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-mu receptors. Dynorphin, an endogenous opioid with a high affinity for the kappa receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at kappa receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury.
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PMID:Neuropeptides in spinal cord injury: comparative experimental models. 665 11


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