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)

1. Whole-cell patch clamp recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid-like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products. 2. Primary and secondary RVM neurons were identified as responding to the kappa-opioid receptor agonist U-69593 (300 nM to 1 microM) and the mu- and delta-opioid receptor agonist met-enkephalin (10 microM), respectively. Both primary and secondary RVM neurons responded to nociceptin (3 nM to 1 microM) with an outward current that reversed polarity at -115 mV in brain slices and with inhibition of Ca(2+) channel currents in acutely isolated cells. 3. The putative ORL1 antagonist J-113397 (1 microM) produced no change in membrane current and abolished the outward current produced by nociceptin (100 nM). In contrast, Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin-(1-13)NH(2) (300 nM to 1 microM) alone produced an outward current and partially reduced the outward current produced by nociceptin (300 nM) when co-applied. 4. In brain slices nociceptin (300 nM) reduced the amplitude of evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) but not non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). 5. Met-enkephalin (10 microM), but not nociceptin (300 nM), reduced the rate of spontaneous miniature IPSCs in normal external potassium solution (K(+) 2.5 mM). In high external potassium (K(+) 17.5 mM), nociceptin reduced the rate of miniature IPSCs in the presence (Ca(2+) 2.4 mM, Mg(2+) 1.2 mM) but not in the absence of external calcium (Ca(2+) 0 mM, Mg(2+) 10 mM, Cd(2+) 10 microM). Nociceptin and met-enkephalin had no effect on the amplitude of miniature IPSCs. 6. The putative nociceptin precursor products nocistatin (rat prepronociceptin(125-132)) and rat prepronociceptin(154-181) had no effect on membrane currents, evoked IPSCs and evoked EPSCs. 7. These results indicate that nociceptin acts via the ORL1 receptor to directly inhibit both primary and secondary RVM neurons by activating a potassium conductance and by inhibiting calcium conductances. In addition, nociceptin inhibits GABA release within the RVM via a presynaptic Ca(2+)-dependent mechanism. Thus, nociceptin has the potential to exert both disinhibitory and inhibitory effects on neuronal action potential firing within the RVM.
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PMID:Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro. 1148 14

1 Patch clamp recordings were made from periaqueductal grey (PAG) neurons in vitro to investigate the cellular actions of opioids in wild-type C57B16/J mice and mutant mice lacking the first exon of the micro -opioid (MOP) receptor. 2 In wild-type mice, the kappa-(KOP) agonist U-69593 (300 nM) and the mixed micro /delta-opioid agonist met-enkephalin (10 micro M), but not the delta-(DOP) agonist deltorphin (300 nM), reduced the amplitude of evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs). Met-enkephalin and U-69593 also reduced the rate of spontaneous miniature IPSCs, but had no effect on their amplitude and kinetics. In micro -receptor-deleted mice, only U-69593 (300 nM) reduced the amplitude of evoked IPSCs. 3 In wild-type mice, the MOP agonist DAMGO (3 micro M) produced an outward current in 76% of the neurons. Deltorphin and U-69593 produced outward currents in 24 and 32% of the neurons, respectively. In micro -receptor-deleted mice, deltorphin and U-69593 produced similar outward currents in 32 and 27% of the neurons, respectively, while DAMGO was without effect. All neurons in both the wild-type and micro -receptor-deleted mice responded with similar outward currents to either the GABA(B) receptor agonist baclofen (10 micro M), or the opioid-like receptor ORL1 (NOP) agonist nociceptin (300 nM). 4 The DAMGO-, deltorphin-, U-69593-, baclofen- and nociceptin-induced currents displayed inward rectification and reversed polarity at -109 to -116 mV. 5 These findings indicate that micro -, delta- and kappa-opioid receptor activation has complex pre- and postsynaptic actions within the mouse PAG. This differs to the rat PAG where only micro -opioid receptor actions have been observed.
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PMID:Cellular actions of opioids on periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1. 1277 Sep 41

Nociceptin/orphanin FQ (N/OFQ), a peptide closely related to dynorphin A, is the endogenous agonist of the NOP receptor that moderately increases food intake under various conditions. Its orexigenic properties are mediated by the brain circuitry. In the present review, we focus on discussing the nature of hyperphagic effects of N/OFQ with special emphasis on its function within feeding-related neural networks. Although some of N/OFQ's orexigenic effects resemble those induced by opioids, reward-dependent feeding appears to be affected in a different manner by agonists of the NOP and classical opioid receptors. Also, data suggest that N/OFQ may not only promote feeding initiation, but rather its role may be to inhibit signaling responsible for inhibition of consummatory behavior. Central systems involved in termination of feeding that seem to be influenced by N/OFQ encompass oxytocin, alpha-MSH, and CRH.
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PMID:Minireview: Characterization of influence of central nociceptin/orphanin FQ on consummatory behavior. 1504 61

Beside the well known actions of opioid peptides on mu-, delta- and kappa-opioid receptors, increasing amount of pharmacological and biochemical evidence has recently been published about non-opioid actions of various opioid peptides. These effects are not abolished by naloxone treatments. Such non-opioid effects are observed both in nervous tissues and in the cellular elements of the immune system. Peptides exhibiting non-opioid effects include beta-endorphin, dynorphin A, nociceptin/OFQ, endomorphins, hemorphins and a number of Proenkephalin A derived peptides, such as Met-enkephalin, Met-enkephalin-Arg-Phe (MERF) and bovine adrenal medullary peptide (BAM22). Non-opioid actions are exerted through different neuronal receptors, e.g., dynorphin hyperalgesia through NMDA receptor, Met-enkephalin induced regulation of cell growth through zeta receptors, pain modulation by nociceptin through ORL-1 or NOP receptors, while BAM22 acts through sensory neuron specific G protein-coupled receptors (SNSR). We have investigated Met-enkephalin-Arg-Phe (MERF) and its analogues by the means of direct and indirect radioligand binding assays. It has been found that in addition to kappa(2) and delta-opioid receptors, MERF can act also through sigma(2)- or probably via FMRF-NH(2) receptors in rat cerebellum. A role of functionally assembling heterodimer receptors in mediating the non-conventional actions of these peptide ligands can not be excluded as well.
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PMID:Non-opioid actions of opioid peptides. 1513 48

Nociceptin/orphanin FQ (N/OFQ), an endogenous agonist of the opioid N/OFQ (NOP) receptor, increases food intake when administered centrally. As N/OFQ is part of a larger neural network that governs consummatory behavior, presumably its orexigenic properties stem from interplay with other neuropeptidergic components of the feeding-related circuitry. One such peptide may be the ligand of the melanocortin-3 and -4 receptors, alpha-melanocyte-stimulating hormone (alpha-MSH), which is known to inhibit food intake. The aim of the present study was to establish whether there is a functional "interaction" between N/OFQ and alpha-MSH in the regulation of feeding. By using double immunostaining for c-Fos and alpha-MSH, we found that intracerebroventricular (i.c.v.) injection of N/OFQ at a 10nmol dose that moderately prolongs deprivation-induced food intake in rats, decreases activation of alpha-MSH neurons involved in feeding termination. However, i.c.v. injections of alpha-MSH at doses previously established to reduce deprivation-induced feeding, do not decrease hyperphagia generated by N/OFQ in ad libitum-fed animals. Our results suggest that while alpha-MSH does not appear to modify the orexigenic response to N/OFQ in sated rats, the NOP receptor ligand promotes a decrease in activation of neurons synthesizing the anorexigenic peptide, alpha-MSH, at the time of re-feeding. Thus, to some degree, the stimulatory effect of N/OFQ on consumption may arise from this peptide's inhibitory influence on activity of anorexigenic pathways containing alpha-MSH.
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PMID:Functional interaction between nociceptin/orphanin FQ and alpha-melanocyte-stimulating hormone in the regulation of feeding. 1658 12

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

In the dorsal raphe nucleus (DRN) many inputs converge and interact to modulate serotonergic neuronal activity and the behavioral responses to stress. The effects exerted by two stress-related neuropeptides, corticotropin releasing factor (CRF) and nociceptin/orphaninFQ (N/OFQ), on the outflow of [(3)H]5- hydroxytryptamine were investigated in superfused rat dorsal raphe nucleus slices. Electrical stimulation (100 mA, 1 ms for 2 min) evoked a frequency-dependent peak of [(3)H]5- hydroxytryptamine outflow, which was sodium and calcium-dependent. Corticotropin releasing factor (1-100 nM), concentration-dependently inhibited the stimulation (3 Hz)-evoked [(3)H]5-hydroxytryptamine outflow; the inhibition by 30 nM corticotropin releasing factor (to 68 +/- 5.7%) was prevented both by the non selective CRF receptor antagonist alpha-helicalCRF(9-41) (alpha-HEL) (300 nM) and by the CRF(1) receptor antagonist antalarmin (ANT) (100 nM). The CRF(2) agonist urocortin II (10 nM) did not modify [(3)H]5- hydroxytryptamine outflow, ruling out the involvement of CRF(2) receptors. Bicuculline (BIC), a GABAA antagonist (10 microM), prevented the inhibitory effect of corticotropin releasing factor (30 nM), supporting the hypothesis that the inhibition was mediated by increased gamma-aminobutyric acid (GABA) release. Nociceptin/ orphaninFQ (1 nM-1 microM) exerted an antalarmin- and bicuculline-insensitive inhibition on [(3)H]5- hydroxytryptamine outflow, with the maximum at 100 nM (to 63+/- 4.2%), antagonized by the NOP receptor antagonist UFP-101 (1 microM). Dorsal raphe nucleus slices prepared from rats exposed to 15 min of forced swim stress displayed a reduced [(3)H]5-hydroxytryptamine outflow, in part reversed by antalarmin and further inhibited by nociceptin/orphaninFQ. These findings indicate that (i) both corticotropin releasing factor and nociceptin/orphaninFQ exert an inhibitory control on dorsal raphe nucleus serotonergic neurons; (ii) the inhibition by corticotropin releasing factor involves gamma-aminobutyric acid neurons; (iii) nociceptin/ orphaninFQ inhibits dorsal raphe nucleus serotonin system in a corticotropin releasing factor- and gamma-aminobutyric acid-independent manner; (iv) nociceptin/orphaninFQ modulation is still operant in slices prepared from stressed rats. The nociceptin/orphaninFQ-NOP receptor system could represent a new target for drugs effective in stress-related disorders.
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PMID:Inhibition of serotonin outflow by nociceptin/orphaninFQ in dorsal raphe nucleus slices from normal and stressed rats: Role of corticotropin releasing factor. 1941 33

Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor (NOP) function in the neuromodulation of anxiety, stress and hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated the endogenous NOP system using the selective NOP antagonist, UFP-101, during the HPA axis response to bacterial endotoxin, lipopolysaccharide (LPS). Although i.c.v. N/OFQ (1 microg/rat) had no significant effect on LPS-induced (250 microg/rat i.p) plasma corticosterone release at 30 or 60 min post-i.c.v. injection, i.c.v. UFP-101 (1 microg/rat)/LPS significantly attenuated plasma adrenocorticotrophic hormone and corticosterone at the 30-min time-point compared to i.c.v saline (0.9%)/LPS. Parvocellular paraventricular nucleus (PVN) corticotrophin-releasing factor (CRF) and corticotrophic pro-opiomelanocortin (POMC), but not parvocellular PVN arginine vasopressin (AVP), mRNA expression was significantly increased by LPS compared to non-LPS control. Intracerebroventricular UFP-101/LPS treatment was associated with increased POMC mRNA expression 4 h after injection and a clear trend towards increased parvocellular CRF mRNA. Furthermore, i.c.v. UFP-101 was selectively associated with an LPS-induced increase in parvocellular AVP mRNA, an effect that was absent in the i.c.v saline/LPS group. To determine whether LPS challenge was associated with compensatory changes in N/OFQ precursor or NOP receptor mRNAs, in a separate study, we undertook reverse transcriptase-polymerase chain reaction analysis of preproN/OFQ and NOP transcripts. In support of an endogenous role for central N/OFQ in inflammatory stress, we found that LPS significantly increased preproN/OFQ transcript expression in the hypothalamus 4 h after injection compared to the saline control. No changes in preproN/OFQ mRNA level in the hippocampus or basal forebrain (including bed nucleus of stria terminalis) were seen, albeit at 4 h. LPS was associated with a significant attenuation of NOP mRNA in the basal forebrain at 4 h, possibly as a compensatory response to increased N/OFQ release. Although the exact mechanisms require elucidation, the findings obtained in the present study provide evidence indicating that the endogenous NOP system is involved in the acute HPA axis response to immune challenge.
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PMID:Endogenous nociceptin / orphanin FQ system involvement in hypothalamic-pituitary-adrenal axis responses: relevance to models of inflammation. 1973 91

Corticotropin releasing factor (CRF) is the primary mediator of stress responses, and nociceptin/orphanin FQ (N/OFQ) plays an important role in the modulation of these stress responses. Thus, in this multidisciplinary study, we explored the relationship between the N/OFQ and the CRF systems in response to stress. Using in situ hybridization (ISH), we assessed the effect of body restraint stress on the gene expression of CRF and N/OFQ-related genes in various subdivisions of the amygdala, a critical brain structure involved in the modulation of stress response and anxiety-like behaviors. We found a selective upregulation of the NOP and downregulation of the CRF1 receptor transcripts in the CeA and in the BLA after body restraint. Thus, we performed intracellular electrophysiological recordings of GABAA-mediated IPSPs in the central nucleus of the amygdala (CeA) to explore functional interactions between CRF and N/OFQ systems in this brain region. Acute application of CRF significantly increased IPSPs in the CeA, and this enhancement was blocked by N/OFQ. Importantly, in stress-restraint rats, baseline CeA GABAergic responses were elevated and N/OFQ exerted a larger inhibition of IPSPs compared with unrestraint rats. The NOP antagonist [Nphe1]-nociceptin(1-13)NH2 increased the IPSP amplitudes in restraint rats but not in unrestraint rats, suggesting a functional recruitment of the N/OFQ system after acute stress. Finally, we evaluated the anxiety-like response in rats subjected to restraint stress and nonrestraint rats after N/OFQ microinjection into the CeA. Intra-CeA injections of N/OFQ significantly and selectively reduced anxiety-like behavior in restraint rats in the elevated plus maze. These combined results demonstrate that acute stress increases N/OFQ systems in the CeA and that N/OFQ has antistress properties.
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PMID:Restraint stress alters nociceptin/orphanin FQ and CRF systems in the rat central amygdala: significance for anxiety-like behaviors. 2440 38