Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Naloxone benzoylhydrazone (NalBzoH) has initially been developed as an agonist of the pharmacologically defined kappa3-opioid receptor and has recently been employed as an antagonist at the opioid receptor-like (ORL1) receptor. In the present study, we investigated the ability of NalBzoH to elicit agonist-like effects on receptor signalling in distinct layers of rat olfactory bulb, a brain region where we have demonstrated the presence of opioid and ORL1 receptors coupled to both stimulation and inhibition of cyclic AMP formation. 2 In membranes of the olfactory nerve-glomerular layer (ON-GL), external plexiform layer (EPL) and granule cell layer (GRL), NalBzoH elicited a concentration-dependent stimulation of guanosine-5'-O-(3-[35S]-thio)triphosphate ([35S]GTPgammaS) binding with pEC50 values ranging from 7.36 to 7.86, whereas the kappa1-opioid receptor agonists (-)-U-50,488 and U-69,593 were inactive. 3 In membranes of GRL, but not ON-GL and EPL, NalBzoH stimulated basal adenylyl cyclase activity by 40% with a pEC50 of 8.14, and significantly potentiated the net enzyme stimulation elicited by corticotropin-releasing hormone and pituitary adenylate cyclase-activating peptide 38. Pertussis toxin prevented the NalBzoH stimulations of [35S]GTPgammaS binding and adenylyl cyclase activity. 4 In membranes of EPL and GRL, but not ON-GL, NalBzoH elicited a concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase activity with pEC50 values of 8.07 and 8.08, respectively. 5 At concentrations that completely blocked the actions of nociceptin/orphanin FQ (N/OFQ), the ORL1 receptor antagonists CompB and [Nphe1]N/OFQ(1-13)NH2 failed to antagonize either the stimulatory or the inhibitory effect of NalBzoH on cyclic AMP formation. Similarly, the kappa1-opioid receptor antagonist nor-binaltorphimine counteracted the NalBzoH effects with relatively low potencies (pKi values=7.67-8.09). 6 Conversely, the selective delta-opioid receptor antagonist TIPP (pKi=9.10) and the selective mu-opioid receptor antagonist CTAP (pKi=8.27) reduced the inhibitory effect of NalBzoH by 70 and 30%, respectively. Moreover, TIPP and CTAP potently inhibited the NalBzoH stimulation of cyclic AMP, each antagonist maximally causing 50% blockade of the agonist response. 7These data demonstrate that in the olfactory bulb NalBzoH activates receptor signalling by acting through delta- and mu-opioid receptors and independently of ORL1 and kappa1-opioid receptors.
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PMID:G protein activation and cyclic AMP modulation by naloxone benzoylhydrazone in distinct layers of rat olfactory bulb. 1545 72

The occurrence of systematic diurnal variations in pain thresholds has been demonstrated in human. Salivary melatonin levels change following acute pain when other factors that could explain the change have been removed or controlled. Melatonin-induced analgesia is blocked by naloxone or pinealectomy. By using selective radioligands [3H]-DAMGO, [3H]-DPDPE, [3-U69593, and 3H]-nociceptin, we have shown that the bovine pinealocytes contain delta and mu, but not kappa or ORL1 opioid receptor subtypes. In the present study, by using melatonin receptor agonists (6-chloromelatonin or 2-iodo-N-butanoyl-5-methoxytryptamine) or melatonin receptor antagonist (2-phenylmelatonin), we have shown that these agents do not compete with opioid receptor subtypes. However, we observed a time-dependent release of beta-endorphin an endogenous opioid peptide, by melatonin from mouse pituitary cells in culture. Hence, it is suggested that melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by binding to its own receptors and increasing the release of beta-endorphin.
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PMID:Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of beta-endorphin an endogenous opioid. 1563 42

The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the precise receptor subpopulations mediating feeding elicited by opioid peptides and agonists as well as homeostatic challenges. The present study examined the dose-dependent (5-80 nmol) cerebroventricular actions of general and selective mu, delta, and kappa1 opioid receptor antagonists together with antisense probes directed against each of the four exons of the MOR-1 opioid receptor gene and each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY-induced feeding was dose-dependently decreased and sometimes eliminated following pretreatment with general, mu, delta, and kappa1 opioid receptor antagonists. Moreover, NPY-induced feeding was significantly and markedly reduced by antisense probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1 gene. Thus, whereas the opioid peptides, beta-endorphin and dynorphin A(1-17) elicit feeding responses that are respectively more dependent upon mu and kappa opioid receptors and their genes, the opioid mediation of NPY-induced feeding appears to involve all three major opioid receptor subtypes in a manner similar to that observed for feeding responses following glucoprivation or lipoprivation.
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PMID:NPY-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats. 1594 35

Two full-length cDNAs, encoding delta (delta) and mu (mu) opioid receptors, were cloned from the brain of the rough-skinned newt Taricha granulosa, complementing previous work from our laboratory describing the cloning of newt brain kappa (kappa) and ORL1 opioid receptors. The newt delta receptor shares 82% amino acid sequence identity with a frog delta receptor and lower (68-70%) identity with orthologous receptors cloned from mammals and zebrafish. The newt mu receptor shares 79% sequence identity with a frog mu receptor, 72% identity with mammalian mu receptors, and 66-69% identity with mu receptors cloned from teleost fishes. Membranes isolated from COS-7 cells transiently expressing the newt delta receptor possessed a single, high-affinity (Kd = 2.4 nM) binding site for the nonselective opioid antagonist [3H]naloxone. In competition binding assays, the newt delta receptor displayed highest affinity for Met-enkephalin, relatively low affinity for Leu-enkephalin, beta-endorphin, and [D-penicillamine, D-penicillamine] enkephalin (DPDPE) (a delta-selective agonist in mammals), and very low affinity for mu-, kappa-, or ORL1-selective agonists. COS-7 cells expressing the newt mu receptor also possessed a high-affinity (Kd = 0.44 nM) naloxone-binding site that showed highest affinity for beta-endorphin, moderate-to-low affinity for Met-enkephalin and Leu-enkephalin and DAMGO (a mu-selective agonist in mammals), and very low affinity for DPDPE and kappa- or ORL1-selective agonists. COS-7 cells expressing either receptor type (delta or mu) showed very high affinity (Kd = 0.1-0.3 nM) for the nonselective opioid antagonist diprenorphine. Taricha granulosa expresses the same four subtypes (delta, mu, kappa, and ORL1) of opioid receptors found in other vertebrate classes, but ligand selectivity appears less stringent in the newt than has been documented in mammals.
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PMID:Delta and mu opioid receptors from the brain of a urodele amphibian, the rough-skinned newt Taricha granulosa: cloning, heterologous expression, and pharmacological characterization. 1637 1

Nociceptin/orphanin FQ (N/OFQ) was identified in 1995 as the endogenous ligand for the orphan G(i)/G(o)-coupled opioid receptor-like 1 receptor (NOP(1)). Exogenous N/OFQ increases food intake in mammals, but its effect and mode of action in chicks are not fully known. We report herein that N/OFQ (5.0 nmol) has a stimulatory effect on food intake in layer-type chicks over a 2-h period after intracerebroventricular (icv) injection. Thirty minutes after central injection of N/OFQ (5.0 nmol) the concentration of agouti-related protein (AGRP) mRNA in the diencephalon increased, while cocaine- and amphetamine-regulated transcript (CART) mRNA decreased. However, concentrations of neuropeptide Y, proopiomelanocortin and glutamate decarboxylase mRNAs, and of catecholamines and excitatory amino acids were not affected. Simultaneous administration of alpha-melanocyte stimulating hormone (alpha-MSH: 1.0 pmol), a competitor of AGRP, completely blocked the orexigenic effect of N/OFQ (5.0 nmol). These data suggest that N/OFQ functions in layer chicks as an orexigenic peptide in the central nervous system, and that the AGRP and the CART neurons may mediate this function, as in mammals.
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PMID:Effect of nociceptin/orphanin FQ on feeding behavior and hypothalamic neuropeptide expression in layer-type chicks. 1931 6


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