Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Dawson-Basoa, Mary E.; Gintzler, Alan R.

doi:10.1016/s0006-8993(96)01334-0

Cited by 44 publications

(10 citation statements)

References 25 publications

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“…Intracerebroventricular administration of orphanin FQ/N in rodents, for example, has been reported to produce enhanced nociception (5, 7), hyperalgesia followed by analgesia (25,26), and a dose-dependent reversal of morphine-induced analgesia (22). A similar variety of neuromodulatory responses, ranging from no detectable effect (27,28) to both analgesia and hyperalgesia (29), has been observed following intrathecal administration of orphanin FQ/N.…”

Section: Discussionmentioning

confidence: 92%

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Danielson

Hoversten

Fitzpatrick³

et al. 2001

Journal of Biological Chemistry

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The elucidation of the cDNA sequence for sturgeon proorphanin provides a unique window for interpreting the evolutionary history of the opioid/orphanin gene family. The molecular "fossil" status of this precursor can be seen in several ancestral sequence characteristics that point to its origin as a duplication of either a prodynorphin-or proenkephalin-like gene. The sturgeon proorphanin cDNA encodes a precursor protein of 194 residues, and the orphanin heptadecapeptide itself binds not only the opioid receptor-like 1 (ORL1) receptor but also the classical (, , and ␦) opioid receptors with near equal affinity. Allowing for this broad receptor specificity are several amino acid substitutions at key positions in the heptadecapeptide sequence, relative to its mammalian orthologs, that have been linked by amino acid scans and site-directed mutagenic studies to the exclusion of mammalian orphanin FQ/nociceptin from classic opioid ligands (i.e. F1Y and L14W). The unique receptor binding profile of sturgeon orphanin not only provides insight into the evolutionary history of the opioid and opioid-related peptides but also provides an ideal context in which to investigate the underlying mechanisms by which novel and often divergent physiological functions arise in receptor-ligand systems.The expansion and functional diversification of multigene families have been a recurring theme in the evolutionary success of complex eukaryotic organisms (1), and the opioid neuropeptides clearly illustrate this phenomenon (2). The classic opioid gene family comprises three neuropeptide precursors encoded on the following genes: proopiomelanocortin (end products: ␤-endorphin, melanocyte-stimulating hormone-associated peptides), proenkephalin (end products: Met-enkephalin, Leuenkephalin), and prodynorphin (end products: dynorphins and ␣-neoendorphin). Based on the organization of these genes it appears that they were derived from a common ancestral gene (3). This hypothesis is supported by the shared neuroinhibitory action of the opioid end products and the selective binding profiles of the opioid peptides to a family of G protein-coupled receptors (, , and ␦ opiate receptors) (4, 5).What has been difficult to resolve is the pattern of evolutionary events that has given rise to the opioid gene family. This is an issue that has been further complicated by the discovery, reported simultaneously by Meunier et al. (6) and Reinscheid et al. (7), of the 17-amino acid orphanin FQ/N, 1 the endogenous ligand for the opioid receptor-like 1 (ORL1) receptor, the "orphan" opiate receptor gene. The organization of the orphanin FQ/N precursor (proorphanin or pronociceptin) indicates that this gene is evolutionarily related to the opioid-coding precursor genes. Mammalian proorphanin has the same basic intronexon structure, conserved N-terminal cysteines, and a modified opioid-like core sequence (FGGF instead of YGGF) that are all defining features of classic opioid precursors. Similarities are also seen at the cellular level where both typical opioids ...

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Section: Discussionmentioning

confidence: 92%

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Danielson

Hoversten

Fitzpatrick³

et al. 2001

Journal of Biological Chemistry

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“…High doses (40 μg) of i.t. nociceptin have also been reported to decrease nociceptive thresholds in rats during late gestation (Dawson‐Basoa & Gintzler, 1997). Thus, low doses of i.t.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological profiles of a novel opioid receptor‐like1 (ORL₁) receptor antagonist, JTC‐801

Yamada¹,

Nakamoto²,

Suzuki³

et al. 2002

British J Pharmacology

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1 Pharmacological eects of a novel opioid receptor-like1 (ORL 1 ) receptor antagonist, [N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride] (JTC-801), were examined in in vitro and in vivo. We have demonstrated that JTC-801 antagonizes the ORL 1 receptor response, and that JTC-801 has ecacious and potent anti-nociceptive eects in acute pain animal models not only by intravenous injection but also oral administration. These results suggest that JTC-801 may represent a new class of analgesics.

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“…In vivo, nociceptin (OFQ) has been variously reported to produce hyperalgesia (Grisel et al, 1996;Mogil et al, l996a,b) or analgesia (Xu et al, 1996;Tian et al, 1997) and appears to modulate opioid-induced analgesia (Grisel et al, 1996;Mogil et al, l996a,b;Tian et al, 1997;Xu et al, 1996;Dawson-Basoa and Gintzler, 1997). Although nociceptin (OFQ) can act functionally as an anti-opioid in vivo, both ORL-l and opioid receptors inhibit cAMP production and activate K channels in a PTXsensitive manner, consistent with G~-mediatedsignal transduction (Meunier et al, 1995;Reinscheid et al, 1995;Conner et al, 1996a,h;Knoflach et al, 1996;Matthes et al, 1996;Vaughan and Christie, 1996;Ma et al.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the ORL-I receptor (OFQR) by intracerebroventricular administration of nociceptin (OFQ) produces hyperalgesia and attenuates the analgesic effects produced by opioid receptor stimulation (Grisel et al, 1996;Mogil et al, l996a,b;Tian et al, 1997). One study demonstrates that intrathecal administration of nociceptin (OFQ) is also capable of inhibiting analgesia (Dawson-Basoa and Gintzler, 1997). In contrast, other studies demonstrate that intrathecal administration of nociceptin (OFQ) produces analgesia (Xu et al, 1996;Tian et al, 1997), or that intrathecal delivery of nociceptin (OFQ) has no effect on morphine-induced analgesia (Grisel et al, 1996).…”

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confidence: 99%

Nociceptin (ORL‐1) and μ‐Opioid Receptors Mediate Mitogen‐Activated Protein Kinase Activation in CHO Cells Through a G_i‐Coupled Signaling Pathway: Evidence for Distinct Mechanisms of Agonist‐Mediated Desensitization

Hawes¹,

Fried²,

Yao³

et al. 1998

Journal of Neurochemistry

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Abstract:The recently identified 17-amino acid peptide nociceptin (orphanin FQ) is the endogenous ligand for the opioid receptor-like-i (ORL-i) receptor. A physiologic role for nociceptin (OFQ) activation of the ORL-1 receptor (OFQR) may be to modulate opioid-induced analgesia. The molecular mechanism by which nociceptin (OFQ) and ORL-1 (OFQR) modify oploid-stimulated effects, however, is unclear. Both ORL-1 (OFQR) and opioid receptors mediate pertussis toxin (PTX)-sensitive signal transduction, indicating these receptors are capable of coupling to GIG0 proteins. This study determines that nociceptin stimulates an intracellular signaling pathway, leading to activation of mitogen-activated protein (MAP) kinase in CHO cells expressing ORL-1 receptor (OFQR). Nociceptin (OFQ)-stimulated MAP kinase activation was inhibited by PTX or by expression of the carboxyl terminus of /3-adrenergic receptor kinase (/3ARKct), which specifically blocks G/3y-mediated signaling. Expression of the proline-rich domain of SOS (SOS-PRO), which inhibits SOS interaction with p21 ras also attenuated nociceptin (OFQ)-stimulated MAP kinase activation. The phosphatidylinositol 3-kinase (P1-3K) inhibitors wortmannm and LY294002 reduced nociceptin (OFQ)-stimulated MAP kinase activation, whereas inhibition of protein kinase C (PKC) activity by bisindolylmaleimide I or cellular depletion of PKC had no effect. In a similar manner, in cells expressing~a-opioid receptor, [D-A1a 2,N-MePhe4 ,Gly-ol] -enkephalin (DAMGO; a p-opioid receptorselective agonist) stimulated PTX-sensitive MAP kinase activation that was inhibited by wortmannin, LY294002, /3ARKct expression, or SOS-PRO expression but not affected by inhibition of PKC activity. These results indicate that both ORL-1 (OFQR) and 1i-opioid receptors mediate MAP kinase activation via a signaling pathway using the /3y-subunit of G, a P1-3K, and SOS, independent of PKC activity. In cells expressing both ORL-i (OFQR) and popioid receptors, pretreatment with nociceptin decreased subsequent nociceptin (OFQ)-or DAMGO-stimulated MAP kinase activation. In contrast, pretreatment of cells with DAMGO decreased subsequent DAMGO-stimulated MAP kinase but had no effect on subsequent nociceptin (OFQ)-stimulated MAP kinase activation. These results demonstrate that nociceptin (OFQ) activation of ORL-i (OFQR) can modulate~a-opioid receptor signaling in a cellular system. Key Words: Nociceptin-p-Opioid receptors-Mitogen-activated protein kinase -GIG0 protein-Pertussis toxin. J. Neurochem. 71, 1024Neurochem. 71, -1033Neurochem. 71, (1998.Nociceptin (orphanin FQ, OFQ) has recently been identified as the endogenous ligand for the orphan opioid receptor-like-I (ORL-l) receptor (Meunier et al., 1995;Reinscheid et al., 1995). The amino acid sequence of the ORL-l receptor (OFQR) is 47% identical to the opioid receptors (~t-, K-, and h-receptors) overall, and is 64% identical in the transmembrane domains (Bunzow et al.,

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Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Cited by 44 publications

References 25 publications

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Pharmacological profiles of a novel opioid receptor‐like1 (ORL₁) receptor antagonist, JTC‐801

Nociceptin (ORL‐1) and μ‐Opioid Receptors Mediate Mitogen‐Activated Protein Kinase Activation in CHO Cells Through a G_i‐Coupled Signaling Pathway: Evidence for Distinct Mechanisms of Agonist‐Mediated Desensitization

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Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Cited by 44 publications

References 25 publications

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Sturgeon Orphanin, a Molecular “Fossil” That Bridges the Gap between the Opioids and Orphanin FQ/Nociceptin

Pharmacological profiles of a novel opioid receptor‐like1 (ORL1) receptor antagonist, JTC‐801

Nociceptin (ORL‐1) and μ‐Opioid Receptors Mediate Mitogen‐Activated Protein Kinase Activation in CHO Cells Through a Gi‐Coupled Signaling Pathway: Evidence for Distinct Mechanisms of Agonist‐Mediated Desensitization

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Pharmacological profiles of a novel opioid receptor‐like1 (ORL₁) receptor antagonist, JTC‐801

Nociceptin (ORL‐1) and μ‐Opioid Receptors Mediate Mitogen‐Activated Protein Kinase Activation in CHO Cells Through a G_i‐Coupled Signaling Pathway: Evidence for Distinct Mechanisms of Agonist‐Mediated Desensitization