Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus

Okuda‐Ashitaka, Emiko; Tachibana, Shinro; Houtani, Takeshi; Minami, Toshiaki; Masu, Yasuo; Nishi, Miyuki; Takeshima, Hiroshi; Sugimoto, Tetsuo; Ito, Seiji

doi:10.1016/s0169-328x(96)00165-9

Cited by 88 publications

(65 citation statements)

References 34 publications

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“…The peptide also a ects nociceptive transmission/perception, inducing either hyperalgesia (Meunier et al, 1995;Reinscheid et al, 1995) or reversal of analgesia mediated or induced by opioids Grisel et al, 1996). Given intrathecally, however, N/OFQ appears to exert a dual e ect comprised of hyperalgesia/ allodynia at low doses and a clear antinociceptive in¯uence at higher doses (Okuda-Ashitaka et al, 1996;Erb et al, 1997;Sakurada et al, 1999). Both of these spinal e ects of N/OFQ are absent in NOP receptor null mutant mice .…”

Section: Introductionmentioning

confidence: 99%

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

Gavioli

Rae

Calò

et al. 2002

British J Pharmacology

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1 Nocistatin (NST) antagonizes several actions of nociceptin/orphanin FQ (N/OFQ), but acts on distinct receptors. As N/OFQ exerts anxiolytic-like actions in various tests, its behavioural actions in the elevated plus-maze (EPM) test were compared with those of bovine NST. 2 Five minutes after i.c.v. treatment, mice were placed on the EPM for 5 min and entries into and time spent on open and closed arms were recorded alongside other parameters. 3 NST (0.1 ± 3 pmol) reduced percentages of entries into (control 39.6+3.1%, peak e ect at 1 pmol NST 8.5+2.9%) and time spent on open arms (control 30.8+2.3%, NST 2.7+1.5%). The C-terminal hexapeptide of NST (NST-C6; 0.01 ± 10 pmol) closely mimicked these actions of NST, with peak e ects at 0.1 pmol. 4 N/OFQ (1 ± 100 pmol) increased percentages of entries into (control 38.5+3.4%; peak e ect at 10 pmol N/OFQ 67.9+4.9%) and time spent on open arms (control 32.0+3.8%; N/OFQ 74.9+5.8%). Closed arm entries, an index of locomotor activity, were unchanged by all peptides. 5 E ects of NST or NST-C6, but not N/OFQ, were still detectable 15 min after injection. Behaviour of animals co-injected with NST (1 pmol) or NST-C6 (0.1 pmol) plus N/OFQ (10 pmol) was indistinguishable from that of controls. 6 These results reveal potent anxiogenic-like actions of NST and NST-C6, and con®rm the anxiolytic-like properties of N/OFQ. As NST and N/OFQ both derive from preproN/OF, anxiety may be modulated in opposing directions depending on how this precursor is processed.

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Section: Introductionmentioning

confidence: 99%

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

Gavioli

Rae

Calò

et al. 2002

British J Pharmacology

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“…We previously showed that intrathecal (i.t.) administration of Noc/OFQ at very low doses (picogram range) induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, as well as hyperalgesia in conscious mice (Okuda-Ashitaka et al, 1996;Hara et al, 1997). On the other hand, i.t.…”

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confidence: 99%

“…The heptadecapeptide called nociceptin/orphanin FQ (hereafter called Noc/OFQ) was identified as an endogenous ligand of the opioid receptor homolog, designated as ORL 1 in humans, and in its rat counterparts as LC132 and ROR-C (Meunier et al, 1995;Reinscheid et al, 1995;Okuda-Ashitaka et al, 1996). Noc/OFQ and its precursor mRNA are found in the superficial dorsal horn of the spinal cord (Okuda-Ashitaka et al, 1996;Ikeda et al, 1998;Neal et al, 1999a;Houtani et al, 2000).…”

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confidence: 99%

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Characterization of Nociceptin/Orphanin FQ-Induced Pain Responses by the Novel Receptor AntagonistN-(4-Amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) Benzamide Monohydrochloride

Muratani

Minami²,

Enomoto³

et al. 2002

J Pharmacol Exp Ther

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At the spinal level, nociceptin/orphanin FQ (Noc/OFQ) produces pronociceptive and allodynic effects at low doses (picogram range), while causing antinociceptive effects at high doses (microgram range). The discrepancy of pain modulation by Noc/OFQ at low and high doses raised a question whether Noc/OFQ exerted actions through the same Noc/OFQ receptor. In the present study, we examined the involvement of the Noc/OFQ receptor in pain responses with the novel nonpeptide antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride (JTC-801). Allodynia and hyperalgesia evoked by intrathecal administration of Noc/OFQ (50 pg/mouse) were dose dependently blocked by simultaneous administration of JTC-801 with IC 50 values of 32.2 and 363 pg, respectively. JTC-801 did not induce allodynia by itself. Subcutaneous injection of formalin into a hindpaw evoked biphasic pain behaviors such as flinching and biting in mice. Noc/OFQ at 10 pg increased the second-phase pain behaviors evoked by 1% formalin, whereas it strongly inhibited both the first-phase and second-phase pain evoked by 2% formalin at 1 g. Although the pronociceptive effect by 10 pg of Noc/OFQ was dose dependently blocked by JTC-801 with an IC 50 value of 4.58 pg, the antinociceptive effects by 1 g of Noc/OFQ were not antagonized by JTC-801. Furthermore, both phases of 2% formalin-induced pain behaviors were relieved by JTC-801. These results demonstrate that pronociceptive responses induced by a low dose of Noc/OFQ may be mediated through the Noc/OFQ receptor in the spinal cord and that JTC-801 can be a useful antagonist to examine the involvement of endogenous Noc/OFQ and mediation of the Noc/OFQ receptor under physiological and pathophysiological conditions including pain.

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“…Total RNA (10 g) was isolated from hTERT-RPE cells with TRIzol (Invitrogen-Life Technologies, Carlsbad, CA), electrophoresed on a 1% agarose-10% formaldehyde gel, transferred to a nylon membrane (Schleicher & Schuell Bioscience, Keene, NH), and then hybridized with 32 P-labeled 785-base-pair (bp) CAT-1, a 760-bp ODC, a 1,020-bp c-myc, and a 228-bp GAPDH cDNA probe. Hybridization was carried out as described previously (35).…”

Section: Methodsmentioning

confidence: 99%

Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells

Kaneko¹,

Okuda‐Ashitaka²,

Andõ³

et al. 2007

American Journal of Physiology-Cell Physiology

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amines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells. Am J Physiol Cell Physiol 293: C729-C737, 2007. First published May 9, 2007 doi:10.1152/ajpcell.00018.2007.-We previously showed that ornithine was mainly transported via cationic amino acid transporter (CAT)-1 in human retinal pigment epithelial (RPE) cell line, human telomerase RT (hTERT)-RPE, and that CAT-1 was involved in ornithine cytotoxicity in ornithine-␦-aminotransferase (OAT)-deficient cell produced by a OAT specific inhibitor, 5-fluoromethylornithine (5-FMO). We showed here that CAT-1 mRNA expression was increased by ornithne in OAT-deficient RPE cells, which was reversed by an inhibitor of ornithine decarboxylase (ODC), ␣-difluoromethylornithine (DFMO). Polyamines, especially spermine, one of the metabolites of ODC, also enhanced the expression of CAT-1 mRNA. ODC mRNA expression was also increased by ornithine and polyamines, and gene silencing of ODC by siRNA decreased ornithine transport activity and its cytotoxicity. In addition, the mRNA of nuclear protein c-myc was also increased in 5-FMO-and ornithinetreated hTERT-RPE cells, and gene silencing of c-myc prevented the induction of CAT-1 and ODC. Increases in expression of CAT-1, ODC, and c-myc, and the inhibition of these stimulated expression by DFMO were also observed in primary porcine RPE cells. These results suggest that spermine plays an important role in stimulation of mRNA expression of CAT-1, which is a crucial role in ornithine cytotoxicity in OAT-deficient hTERT-RPE cells. ornithine transport; ornithine decarboxylase; c-myc

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Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus

Cited by 88 publications

References 34 publications

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

Characterization of Nociceptin/Orphanin FQ-Induced Pain Responses by the Novel Receptor AntagonistN-(4-Amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) Benzamide Monohydrochloride

Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells

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