Biochemical Evidence for Orphanin FQ/Nociceptin Receptor Heterogeneity in Mouse Brain

Mathis, John P.; Ryan-Moro, Jennifer P.; Chang, Albert; Hom, Judith S.H.; Scheinberg, David A.; Pasternak, Gavril W.

doi:10.1006/bbrc.1996.5867

Cited by 116 publications

(65 citation statements)

References 13 publications

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“…B max and K D values in rat cerebrocortical membranes (from our previous report, Okawa et al, 1998) were consistent with others using the same radioligand (Ardati et al, 1997). Slope factors were close to unity in both reports and suggest that [ 125 I]-Tyr 14 -NC is binding to a single class of receptors although Mathis et al (1997) reported both high and low a nity binding sites in mouse brain membranes. B max in CHO NCR cell membranes was consistent with others (Fawzi et al, 1997) while it was slightly higher than those of Reinscheid et al (1996) and Ardati et al (1997) using the same radioligand.…”

Section: Discussionsupporting

confidence: 90%

“…Butour et al (1997) and Adapa & Toll (1997) reported values similar to ours using [ 3 H]-NC and [ 3 H]-Tyr 14 -NC, respectively. In this study we observed binding slope factors close to unity in CHO NCR cell membranes, again suggesting a single binding site in accordance with others (Reinscheid et al, 1996;Ardati et al,1997, Adapa & Toll, 1997Mathis et al, 1997). Adapa & Toll (1997) conducted binding experiments using intact CHO NCR cells in physiological bu er similar to that used for our cyclic AMP assay.…”

Section: Discussionsupporting

confidence: 89%

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Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Okawa

Nicol

Bigoni

et al. 1999

British J Pharmacology

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Nociceptin(NC) is the endogenous ligand for the opioid receptor like‐1 receptor (NC‐receptor). [Phe1ΨC(CH2‐NH)Gly2]Nociceptin(1–13)NH2 ([F/G]NC(1–13)NH2) has been reported to antagonize NC actions in peripheral guinea‐pig and mouse tissues. In this study, we investigated the effects of a range of NC C‐terminal truncated fragments and [F/G]NC(1–13)NH2 on NC receptor binding, glutamate release from rat cerebrocortical slices (rCX), inhibition of cyclic AMP accumulation in CHO cells expressing the NC receptor (CHONCR) and electrically evoked contractions of the rat vas deferens (rVD). In radioligand binding assays, a range of ligands inhibited [125I]‐Tyr14‐NC binding in membranes from rCX and CHONCR cells. As the peptide was truncated there was a general decline in pKi. [F/G]NC(1–13)NH2 was as potent as NC(1–13)NH2. The order of potency for NC fragments to inhibit cyclic AMP accumulation in whole CHONCR cells was NCNH2NC=NC(1–13)NH2>NC(1–12)NH2>>NC(1–11)NH2. [F/G]NC(1–13)NH2 was a full agonist with a pEC50 value of 8.65. NCNH2 and [F/G]NC(1–13)NH2 both inhibited K+ evoked glutamate release from rCX with pEC50 and maximum inhibition of 8.16, 48.5±4.9% and 7.39, 58.9±6.8% respectively. In rVD NC inhibited electrically evoked contractions with a pEC50 of 6.63. Although [F/G]NC(1–13)NH2, displayed a small (instrinsic activity α=0.19) but consistent residual agonist activity, it acted as a competitive antagonist (pA2 6.76) in the rVD. The differences between [F/G]NC(1–13)NH2 action on central and peripheral NC signalling could be explained if [F/G]NC(1–13)NH2 was a partial agonist with high strength of coupling in the CNS and low in the periphery. An alternative explanation could be the existence of central and peripheral receptor isoforms. British Journal of Pharmacology (1999) 127, 123–130; doi:10.1038/sj.bjp.0702539

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Okawa

Nicol

Bigoni

et al. 1999

British J Pharmacology

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“…This view is further supported by our present ®nding that [Tyr 14 ]-nociceptin (identi®ed as a potent ORL 1 receptor ligand by Reinscheid et al, 1995;Berzetei-Gurske et al, 1996;Shimohigashi et al, 1996;Mathis et al, 1997) mimicked the e ect of nociceptin, in a manner sensitive to naloxone benzoylhydrazone. As expected, [des-Phe 1 ]-nociceptin, a degradation product of nociceptin (Montiel et al, 1997), failed to mimic the e ect of nociceptin.…”

Section: Discussionsupporting

confidence: 63%

“…Thus, the a nity/potency of [Tyr 14 ]-nociceptin did not exceed that of nociceptin both at the ORL 1 receptor of the mouse vas deferens (Berzetei-Gurske et al, 1996) and in a binding study on mouse brain membranes, using [ 125 I]-[Tyr 14 ]-nociceptin (Mathis et al, 1997). The reason for the discrepancies is unclear but one has to consider that the functional ORL 1 receptors in the cerebral cortex and in the vas deferens of the mouse di er with respect to the liability to desensitization (see later) and were identi®ed under very di erent experimental conditions (i.e.…”

Section: Discussionmentioning

confidence: 92%

Further characterization of the ORL₁ receptor‐mediated inhibition of noradrenaline release in the mouse brain in vitro

Werthwein

Bauer

Nakazi

et al. 1999

British J Pharmacology

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In conclusion, nociceptin inhibits noradrenaline release in the mouse cortex via ORL 1 receptors, which interact with presynaptic a 2 -autoreceptors on noradrenergic neurones. The e ect of nociceptin does not desensitize nor does it involve NO, prostanoids or adenosine. Nociceptin also attenuates noradrenaline release from several subcortical regions and serotonin release from cortical slices by a naloxone benzoylhydrazone-sensitive mechanism.

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“…5) Radioligand binding studies of the ORL1 receptor have been performed in brain tissues of rats, humans, mice, frogs and Chinese hamster ovary (CHO) cells expressing ORL1 receptors. [22][23][24][25] However, to our knowledge, little information has been published on ORL1 receptor characteristics in the spinal cord. It is considered that this tissue may play a significant role in the appearance of allodynia and antinociception by nociceptin.…”

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confidence: 99%

Characterization of Specific [3H]Nociceptin Binding in Rat Brain and Spinal Cord.

Kusaka

Yamada

Kimura

2001

Biological & Pharmaceutical Bulletin

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Nociceptin (orphanin FQ), a heptadecapeptide isolated from rat and porcine brain, has been identified as the endogenous ligand of opioid receptor-like ORL1 receptor, an orphan G protein-coupled receptor. 1,2) The sequences of human, mouse and rat complementary DNA for the ORL1 receptor indicate a significant degree of homology with the 'classical opioid' receptors (m, d and k). [3][4][5][6][7] In spite of this homology with opioid receptors, potent opioid ligands fail to bind to ORL1 receptors. Nociceptin itself has high homology with opioid peptides, particularly dynorphin A, the endogenous ligand of the k-opioid receptor, but this peptide exhibits very low binding affinity for opioid receptors. 8) Pharmacological studies have shown that nociceptin may be involved in a wide variety of physiological functions: pain and analgesia, 9) opioid tolerance, 10) learning and memory, 11) locomotion, 12) feeding, 13) stress and anxiety 14) and neuronal differentiation 15) in the central nervous system. It may also produce effects on the cardiovascular system, 16,17) urogenital tract 18,19) and immune system 20) in the periphery. It is of interest to note that local microinjection of nociceptin into brain and spinal cord of rats and mice produces opposite effects on the nociceptive response. 21) In relation to these effects, the ORL1 receptor has been suggested to be present in the brain and spinal cord following in situ hybridization analysis, 4,6) and in peripheral tissues such as the intestine, vas deferens, liver and spleen. 5) Radioligand binding studies of the ORL1 receptor have been performed in brain tissues of rats, humans, mice, frogs and Chinese hamster ovary (CHO) cells expressing ORL1 receptors. [22][23][24][25] However, to our knowledge, little information has been published on ORL1 receptor characteristics in the spinal cord. It is considered that this tissue may play a significant role in the appearance of allodynia and antinociception by nociceptin. Thus, the aim of the present study was to characterize specific [ 3 H]nociceptin binding simultaneously in rat brain and spinal cord. Further, the distribution of ORL1 receptors in the rat brain was examined. Tissue Preparation Male Sprague-Dawley rats (200-300 g) at 7-8 weeks of age were sacrificed by decapitation and the whole brain and spinal cord were removed. To study the distribution of specific binding of [ 3 H]nociceptin, cerebral cortex, corpus striatum, hippocampus, thalamus, pons/medulla oblongata, midbrain and cerebellum were dissected. The tissues (whole brain and spinal cord) were homogenized in 19 volumes of ice-cold 50 mM Tris-HCl buffer (pH: 7.4) containing 2 mM EDTA, 0.1 mM ( p-amidinophenyl)methanesulfonyl fluoride hydrochloride ( p-APMSF) (buffer A) 26) using a Polytron homogenizer, and the homogenate was centrifuged at 500ϫg for 10 min. The supernatant was centrifuged at 40000ϫg for 15 min. The pellet was finally suspended in ice-cold buffer A containing 2 mg/ml bovine serum albumin (buffer B) and used in [ 3 H]nociceptin binding assays. Al...

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Biochemical Evidence for Orphanin FQ/Nociceptin Receptor Heterogeneity in Mouse Brain

Cited by 116 publications

References 13 publications

Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Further characterization of the ORL₁ receptor‐mediated inhibition of noradrenaline release in the mouse brain in vitro

Characterization of Specific [3H]Nociceptin Binding in Rat Brain and Spinal Cord.

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Biochemical Evidence for Orphanin FQ/Nociceptin Receptor Heterogeneity in Mouse Brain

Cited by 116 publications

References 13 publications

Comparison of the effects of [Phe1Ψ(CH2‐NH)Gly2]Nociceptin (1–13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Comparison of the effects of [Phe1Ψ(CH2‐NH)Gly2]Nociceptin (1–13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Further characterization of the ORL1 receptor‐mediated inhibition of noradrenaline release in the mouse brain in vitro

Characterization of Specific [3H]Nociceptin Binding in Rat Brain and Spinal Cord.

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Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Comparison of the effects of [Phe¹Ψ(CH₂‐NH)Gly²]Nociceptin (1–13)NH₂ in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors

Further characterization of the ORL₁ receptor‐mediated inhibition of noradrenaline release in the mouse brain in vitro