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 a rat tail-flick analgesic assay that uses a cold water-ethylene glycol mixture (-10 degrees C) as the noxious stimulus, we have been able to demonstrate a dose-related, naloxone-reversible analgesic effect for dynorphin A (1-17), the proposed endogenous ligand for the kappa receptor. Male Sprague-Dawley rats were implanted surgically with cannulas in the right lateral ventricle at least 1 week before testing. Five microliters of either drug or saline, followed by a 3-microliter saline flush, were administered. Nociceptive threshold was measured as the latency for the rat to flick or remove its tail from the bath solution after immersion. Dynorphin produced a dose-related analgesia at doses of 1 to 50 micrograms i.c.v., reaching 100% maximum possible analgesia (compared to predrug base line) at the highest dose. We found similar dose-related analgesia when we tested the selective mu agonist [Try-D-Ala-Gly-NMe-Phe-Gly-ol] (0.01-1 microgram), the selective kappa receptor ligand U-50,488H (100-500 micrograms), the selective delta agonist [D-Pen2,5]-enkephalin (50-200 micrograms) and beta-endorphin (0.1-10 micrograms). Naloxone (1.0 mg/kg) was able to block the antinociceptive effect of all but the highest doses of dynorphin, which required 10.0 mg/kg of naloxone. When we compared the same dosages of dynorphin using hot water (55 degrees C) as the noxious stimulus, no antinociception was observed. Although we do not known the mechanisms responsible for the differences between the hot and cold water tests, it may be that the cold water tail-flick test, which is able to assess the antinociceptive activity of both opioid agonists and mixed agonist-antagonists, is a more sensitive measure of the type of analgesia mediated by kappa receptors.
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PMID:Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat. 290 Mar 24

The effects of opioid peptides that are highly selective ligands for mu receptors (morphiceptin). delta receptors (delta-receptor peptide), kappa receptors (dynorphin 1-9), and the mu/delta complex (beta-endorphin), were tested on lordosis behavior in ovariectomized rats primed with estrogen and progesterone. Intracerebroventricular infusions of beta-endorphin or morphiceptin both inhibited and facilitated lordosis in a dose-dependent fashion whereas all doses of delta-receptor peptide facilitated lordosis. Dynorphin 1-9 had no significant effect at any dose, although a trend toward increased lordosis quotients was observed 30 min after infusion. The effects of beta-endorphin, morphiceptin, and delta-receptor peptide were reversed with naloxone, although naloxone alone had no effect on lordosis behavior. These results indicate that the specific activation of opioid receptor subtypes differentially affects lordosis behavior. It appears that binding to high-affinity mu 1 receptors exerts an inhibitory influence on lordosis, whereas binding to low-affinity mu 2 receptors or delta receptors exerts a facilitatory influence. Binding to kappa receptors does not appear to affect lordosis behavior.
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PMID:Selective activation of opioid receptors differentially affects lordosis behavior in female rats. 303 14

Endogenous opioid peptides have been implicated in stress-induced analgesia and stress-induced feeding behavior. An earlier study from our laboratory showed that rats subjected to cold swim stress consumed significantly more food compared to controls. The present study describes changes in the levels of various opioid peptides in the central nervous system and periphery due to cold swim stress. Male Sprague-Dawley rats were subjected to cold swim stress (1 degree C for 5 min), then sacrificed by decapitation; brain, pituitary, adrenals and plasma were collected. Tissue extracts were assayed for opioid peptides by RIA. Cold swim stress resulted in analgesia which could be blocked by prior administration of naloxone, as observed by a tail-flick latency test. Cold swim stress caused a 42% decrease in pituitary beta-endorphin, but increased the level of this peptide in the hypothalamus and plasma by 36% and 337%, respectively. Dynorphin level decreased by 62% in the hypothalamus, but was not affected in the pituitary. Levels of Leu-enkephalin and Met-enkephalin decreased in the adrenal gland by 37% and 18%, respectively, but were not significantly affected in the CNS. These results indicate that cold swim stress has a differential effect on the level of CNS and peripheral opioid peptides, and that both central and peripheral opioid peptides may be important in stress-induced analgesia and feeding behavior.
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PMID:Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. 335 22

Immunohistochemistry of peptide- and dopamine-beta-hydroxylase-(DBH)-containing varicose nerve fibres and ganglion cells, respectively, in the guinea pig inferior mesenteric ganglion was investigated following a) transsection of mesenteric (colonic) branches, b) transsection of central (lumbar splanchnic, intermesenteric and hypogastric) branches, and c) transplantation into the spleen. The findings indicate that pathways of different opioid peptides are not identical. Met-enkephalin- and met-enkephalin-arg-phe- (cleavage products from pre-proenkephalin) containing fibres course in central branches to make contact in the inferior mesenteric ganglion. Dynorphin- and alpha-neo-endorphin- (deriving from pre-prodynorphin) containing fibres as well as leu-enkephalin- (included in the dynorphin sequence) fibres appear to rise not only from central and from enteric somata, but also from intraganglionic noradrenergic neurons. Similar pathways seem to be used by VIP- and by neurotensin-immunoreactive fibres, although intraganglionic neurotensin-immunoreactive cell bodies are rare. Practically all substance P- and most CGRP-immunoreactive fibres enter the ganglion via central branches and, to a large extent, traverse it, but some CGRP-immunoreactive influx appears to come from the intestine. The origin of intraganglionic substance P- and CGRP-immunoreactive fibres after ganglion transplantation remained unidentified. Somatostatin- and neuropeptide Y-immunoreactive fibres predominantly have an intraganglionic origin as have DBH-immunoreactive noradrenergic fibres. The demonstrated alterations in neuropeptide immunoreactivity of intraganglionic and periganglionic nerve fibres following the applied transsection procedures contribute to the present knowledge on origin and destination of peptidergic transmitter segments in the guinea pig inferior mesenteric ganglion. Moreover, the present study provides evidence that intrinsic participation in intraganglionic fibre supply is more extensive than hitherto believed.
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PMID:Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations. 336 35

The involvement of opioid peptides in the regulation of food intake has been postulated. However, it is not known how they are involved in this regulation and which brain region is responsible for the mediation of their effects. We studied the effect of a microinjection of opioid agonists and antagonists into the nucleus accumbens septi (NAS) on the food intake in rats, as this area is known to be important for motivation. Male Wistar rats were implanted stereotaxically with guide cannulae. Rats were not allowed food prior to drug treatment and solutions (1 microliter) were microinjected bilaterally. Food intake was measured throughout a 2 hr period after the drug injection. Infusions into the NAS of 2, 5 and 10 nmol of morphine, D-ala2, D-Leu5-enkephalin (DADLE), and beta-endorphin (beta E), or of 5 and 10 nmol of alpha-neoendorphin (ANEO) induced a dose-dependent increase in the food intake. Dynorphin (DYN) also increased the food intake, but only at a 10 nmol dose. The new, highly selective delta agonist D-Pen2,5-enkephalin (DPDPE) induced a dose-dependent increase in the food intake. Naloxone in doses of 2 and 10 nmol antagonized the increased food intake induced by morphine, beta E, ANEO and DYN in a dose-dependent manner, but only partly antagonized the effect of DADLE on the food intake. The selective mu-receptor antagonist beta-funaltrexamine (beta-FNA), in a dose of 5 nmol completely blocked the increase in the food intake induced by morphine but not by DADLE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats. 379 37

A soluble metalloendopeptidase identified in rat brain, preferentially cleaves bonds in peptides having hydrophobic amino acid residues in the P1, P2, and P3' positions. (The nomenclature of T. Schechter and A. Berger is used to describe the interaction between enzyme and substrate. The amino acid residues in the substrate are designated as P1, P2, P3 etc. in the N-terminal direction and P1', P2', P3' etc. in the C-terminal direction from the bond undergoing cleavage. The corresponding subsites in the enzyme are identified by the letter S.) The degradation of a series of biologically active peptides and their affinity toward the enzyme was studied. Dynorphin-(1-8), alpha-neo-endorphin, and beta-neo-endorphin are rapidly hydrolyzed to form leu-enkephalin, whereas bovine adrenal medulla dodecapeptide is hydrolyzed to form met-enkephalin. The enzyme, however, does not cleave a larger precursor molecule of metenkephalin, such as bovine adrenal medulla docosapeptide. Several other bioactive peptides are also cleaved at sites consistent with our previously reported specificity studies. Met- and leu-enkephalin are resistant to hydrolysis. The binding affinity [as expressed by inhibitory constant (Ki) or Michaelis-Menten constant (Km) values] of several bioactive peptides such as dynorphin-(1-8), beta-neo-endorphin, neurotensin, angiotensin I, and bradykinin was found to be in the micromolar range. These peptides were also rapidly hydrolyzed by the enzyme, showing, as a result, high specificity constants (kcat/Km values). The highest enzyme activity was found in brain, testis, and in the anterior and posterior lobes of the pituitary, while the activity in such tissues as spleen, liver, kidney, lung, adrenals, and thyroid amounted to only 10-20% of that found in brain. This distribution of enzyme activity, together with its preference for oligopeptides as substrates, its ability to generate leu- and met-enkephalin from several larger peptide precursors, and its affinity toward several other bioactive peptides, suggests that the enzyme functions in the metabolism of neuropeptides.
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PMID:Soluble metalloendopeptidase from rat brain: action on enkephalin-containing peptides and other bioactive peptides. 388 8

gamma-Endorphin generating endopeptidase (gamma EGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18-31). The inhibitory potency on gamma EGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1-13) (IC50: 0.14 microM), human beta-endorphin-(1-31) (IC50: 15.5 microM), porcine ACTH-(1-39) (IC50: 6.3 microM), and substance P (IC50: 26 microM) had an inhibitory activity on gamma EGE activity. beta-Endorphin-(18-31) (IC50: 0.35 microM) but not gamma-endorphin potently inhibited gamma EGE activity. The IC50 of poly (Lys)40-60 was 0.8 microM. It is concluded that 1) gamma EGE activity is strongly inhibited by its product beta-endorphin-(18-31), 2) the enzyme is strongly inhibited by peptides with an aromatic amino acid at the NH2-terminal and/or basic amino acids in the COOH-terminal of the peptide chain.
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PMID:Inhibition of gamma-endorphin generating endopeptidase activity of rat brain by peptides: structure activity relationship. 391 46

Adult female rats were implanted with permanent cannulae in the third ventricle of the brain and ovariectomized. 3 weeks later, blood samples were withdrawn every 5 min from intraatrial cannulae placed the previous day. After a control sampling period of 30 min, the rats received an intraventricular bolus injection of saline (2 microliter) or beta-endorphin (beta E; 10 micrograms); sampling was continued for an additional 2 h. Saline injection caused no effect on luteinizing hormone (LH) and prolactin (PRL) secretion. beta E stimulated PRL secretion within 5-10 min, the values peaked in the next 10 min. Thereafter, as PRL levels fell, a suppression of LH secretion became apparent. Inhibition of LH release started 20-35 min after beta E injection and lasted for 35-65 min. The antecendent PRL secretion was apparently not responsible for the observed delayed LH response, since blockade of PRL response with bromocriptine failed to affect the beta E-induced LH suppression. Further, continuous intraventricular infusion of beta E (5 or 10 micrograms/h) for 3 h markedly suppressed the amplitude and frequency of LH episodes in long-term ovariectomized rats. Bolus intraventricular injection of other endogenous opioid peptides and opiate receptor agonists produced different PRL and LH responses. Dynorphin (10 micrograms) similarly suppressed LH release but was only moderately effective in stimulating PRL. Leucine enkephalin (50 micrograms) stimulated LH and inhibited PRL release, while methionine-enkephalin (50 micrograms) selectively stimulated PRL release. The methionine-enkephalin analogs, FK-33824 (50 ng) and DALAMID (50 micrograms), evoked sequential PRL and LH responses similar to those seen after beta E injection. Interestingly, morphiceptin (a specific mu receptor agonist; 10 micrograms) markedly suppressed LH release, but only sparingly stimulated PRL release. Delta receptor peptide (a specific delta receptor agonist; 10 micrograms) selectively suppressed LH release. Bremazocine (a specific kappa receptor agonist; 0.5 mg/kg) administered intravenously suppressed LH release selectively. These studies show that of the four endogenous opioid peptides tested beta E was most effective in evoking sequential PRL and LH responses, and these effects may be mediated by either epsilon receptors or multiple opiate receptor subtypes; stimulation of kappa receptors by bynorphin or bremazocine suppressed LH release, and further studies would be needed to understand the mode of action of the two enkephalins and the delta opiate receptors in eliciting disparate PRL and LH responses.
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PMID:Effects of endogenous opioid peptides and opiates on luteinizing hormone and prolactin secretion in ovariectomized rats. 404 42

Dynorphin-(1-13), but not dynorphin-(1-9) has been shown to have significant effects on opiate and beta-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin had no effect on Sandoz FK33824 compound-induced analgesia.
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PMID:Dynorphin: a possible modulatory peptide on morphine or beta-endorphin analgesia in mouse. 611 61

In previous studies, we observed that dynorphin- (1-13), but not dynorphin-(1-9), can significantly inhibit morphine- or beta-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin-(1-13) showed no inhibitory effect on Sandoz FK33824-induced analgesia. In the present study, we examined the effect of dynorphin on morphine-, beta-endorphin-, D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia in both naive, morphine-tolerant and morphine-dependent mice. It was found that although dynorphin may inhibit morphine- or beta-endorphin-induced analgesia in naive animals, the peptide is not effective in inhibiting D-ala2-D-leu5-enkephalin- or Sandoz FK33824-induced analgesia. Dynorphin is also effective in blocking spontaneous withdrawal jumping in morphine-dependent animals. It is suggested that dynorphin-(1-13) may play a modulatory role in regulating analgesia due to morphine or beta-endorphin, but not that due to enkephalin. The action of peptides on morphine- or beta-endorphin-induced analgesia in the naive state is different from that of the tolerant state, suggesting that dynorphin may be involved in the development of morphine tolerance and physical dependence.
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PMID:Possible regulatory role of dynorphin on morphine- and beta-endorphin-induced analgesia. 611 98


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