Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a μ, δ or κ opioid receptor type

Bunzow, James R.; Sáez, Carmen; Mortrud, Marty; Bouvier, C.; Williams, John T.; Low, Malcolm J.; Grandy, David K.

doi:10.1016/0014-5793(94)00561-3

Cited by 565 publications

(355 citation statements)

References 19 publications

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“…Like (x, 8, and K opioid receptors, the newly discovered ORLi is also widely expressed throughout the brain and spinal cord as detected by Northern blotting, in situ hybridization and immunohistochemistry [2,3,5,18]. The expression of ORLi overlaps with that of other opioid receptors in many regions of the central nervous system.…”

Section: Discussionmentioning

confidence: 93%

“…These opioid receptors are all coupled to the inhibitory G protein (Gi) and negatively regulate adenylyl cyclase [1]. Recently, another Gi protein coupled receptor, opioid receptor-like receptor (ORLi), has been cloned from brain [2][3][4][5][6][7][8]. Its endogenous specific agonist nociceptin/orphanin FQ (OFQ) has also been identified [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

Cheng

Fan

et al. 1997

FEBS Letters

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

Cheng

Fan

et al. 1997

FEBS Letters

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“…A G-protein-coupled receptor, previously known as ORL 1 (Opioid Receptor-Like 1) now known as OP 4 /nociceptin (Hamon, 1998;Calo' et al, 2000a,b), which is sequentially homologous with opioid (OP) receptors but not activated by known opioid ligands, has recently been identi®ed and cloned (Bunzow et al, 1994;Chen et al, 1994;Mollereau et al, 1994). An endogenous agonist for OP 4 /nociceptin receptors was later identi®ed (Meunier et al, 1995;Reinscheid et al, 1995) and named orphanin FQ or nociceptin.…”

Section: Introductionmentioning

confidence: 99%

[Nphe¹]‐Nociceptin (1‐13)‐NH₂, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats

Redrobe

Calò

Guerrini

et al. 2000

British J Pharmacology

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1 The present study was undertaken to investigate the e ects of the novel nociceptin receptor antagonist, [Nphe 1 ]-Nociceptin (1-13)-NH 2 (bilateral intrahippocampal injection, 50 nmole rat 71 ) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat 71 ) de®cits in spatial learning in the rat Morris water maze task. In addition, experiments were performed in an`open ®eld' to investigate possible peptide-induced changes in exploratory behaviour. 2 Nociceptin signi®cantly impaired the ability of the animal to locate the hidden platform throughout training (P50.001 versus control group). 3 Pretreatment with [Nphe 1 ]-Nociceptin (1-13)-NH 2 signi®cantly blocked nociceptin-induced impairment of spatial learning (P50.001 versus nociceptin group). 4 A probe trial revealed that vehicle-treated animals spent more time in the quadrant that had previously contained the hidden platform, whereas nociceptin-treated animals did not spend more time in any one quadrant. 5 Learning impairments were not attributable to non-speci®c de®cits in motor performance or change in exploratory behaviour. 6 Taken together, our results reveal that [Nphe 1 ]-Nociceptin (1-13)-NH 2 represents an e ective and useful in vivo antagonist at the nociceptin receptors involved in learning and memory.

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“…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.…”

mentioning

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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Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a μ, δ or κ opioid receptor type

Cited by 565 publications

References 19 publications

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

[Nphe¹]‐Nociceptin (1‐13)‐NH₂, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats

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

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Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a μ, δ or κ opioid receptor type

Cited by 565 publications

References 19 publications

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL1 in neuroblastoma×glioma NG108‐15 hybrid cells

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL1 in neuroblastoma×glioma NG108‐15 hybrid cells

[Nphe1]‐Nociceptin (1‐13)‐NH2, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats

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

Contact Info

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Resources

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Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

Functional expression, activation and desensitization of opioid receptor‐like receptor ORL₁ in neuroblastoma×glioma NG108‐15 hybrid cells

[Nphe¹]‐Nociceptin (1‐13)‐NH₂, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats