Autoradiographic localization of [3H]nociceptin binding sites from telencephalic to mesencephalic regions of the mouse brain

Florin, Sébastien; Leroux-Nicollet, Isabelle; Meunier, Jean‐Claude; Costentin, Jean

doi:10.1016/s0304-3940(97)00470-9

Cited by 52 publications

(27 citation statements)

References 20 publications

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“…Dooley et al (1997) also demonstrated a close structure-activity relationship around the linear hexapeptide. In vitro receptor autoradiography with [ 3 H]ac-RYYRWK-NH 2 to rat brain sections revealed that the pattern of distribution as well as the actual densities paralleled well with what has been observed with [ 3 H]NC in the present study and with a previous study using mouse brain (Florin et al 1997). These data further demonstrated that [ 3 H]ac-RYYRWK-NH 2 is a highly selective ligand for ORL1, labelling no additional high affinity sites in the rat brain.…”

Section: Discussionsupporting

confidence: 91%

[ 3 H]ac-RYYRWK-NH 2 , a novel specific radioligand for the nociceptin/orphanin FQ receptor

Thomsen

Valsborg

Platou

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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The hexapeptide ac-RYYRWK-NH2 has been described as a potent partial agonist at the nociceptin (NC)/orphanin FQ receptor which has no affinity for mu-, kappa- or delta-opioid receptors. However, it is not clear whether ac-RYYRWK-NH2 is truly selective for the NC receptor, and ac-RYYRWK-NH2 has therefore been radiolabelled and characterised in receptor-binding experiments. Saturation experiments with [3H]ac-RYYRWK-NH2 binding to rat cortical membranes revealed a single high affinity site for [3H]ac-RYYRWK-NH2 (Kd=0.071 +/- 0.018 nM; Bmax=22+/-2 fmol/mg protein). Uncoupling of the G-proteins resulted in a significant 45% increase in Kd and no change in Bmax. [3H]ac-RYYRWK-NH2 binding to rat cortical membranes or to membranes from baby hamster kidney cells expressing human orphan opioid receptor-like (ORL1) was displaced by NC and ac-RYYRWK-NH2 to the same extent. The following rank order of potency was observed: ac-RYYRWK-NH2 > [Tyr14]NC-OH = NC-OH = NC-NH2 > NC, H-(1-13)-NH2 > NC(1-12)-NH2 >> NC(1-11)-NH2 and, thus, displayed a typical NC receptor pharmacology. Novel cyclic analogues of ac-RYYRWK-NH2 were prepared but these structures were much less active when compared to ac-RYYRWK-NH2. In vitro receptor autoradiography with [3H]ac-RYYRWK-NH2 to rat brain sections revealed high levels of binding in the cerebral cortex, amygdala, hypothalamus and superior colliculus, but low levels in the cerebellum and striatum. Overall, the regional distribution was very similar to that of [3H]NC. Ac-RYYRWK-NH2 seems indeed to be selective for the NC receptor and [3H]ac-RYYRWK-NH2 is a novel radioligand which may be useful for further exploring the pharmacology and receptor-ligand interaction of the NC receptor.

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Section: Discussionsupporting

confidence: 91%

[ 3 H]ac-RYYRWK-NH 2 , a novel specific radioligand for the nociceptin/orphanin FQ receptor

Thomsen

Valsborg

Platou

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…In addition, activation of enkephalin-containing CA1 perforant projections or local opioid-containing interneurons are believed responsible for a naloxone sensitive LTD in area CA1 (Francesconi et al 1997). Considering the highly abundant presence of ORL-1 receptors (Lachowicz et al 1995;Anton et al 1996;Florin et al 1997) as well as µ and ␦ opioid receptors (Mansour et al 1987) in the hippocampus, the interaction between these two peptide systems could have significant influence on the modulation of hippocampal plasticity. In this context, the bidirectional action of OFQ, when operating together with endogenous µ/␦ opioids or other plasticity enhancers, may provide an efficient means for adjusting the direction and magnitude of plastic changes in synaptic connection, thereby increasing the flexibility and maximal capacity of the system as a whole.…”

Section: And L E a R N I N G M E M O R Ymentioning

confidence: 99%

Orphanin FQ Suppresses NMDA Receptor-Dependent Long-Term Depression and Depotentiation in Hippocampal Dentate Gyrus

Wei

Xie²

1999

Learn. Mem.

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We reported previously that orphanin FQ (OFQ) inhibited NMDA receptor-mediated synaptic currents and consequently suppressed induction of long-term potentiation (LTP) in the hippocampal dentate gyrus. This study examines the effect of OFQ on several other forms of long-term synaptic plasticity in the lateral perforant path of mouse hippocampal dentate gyrus. high-frequency train-induced dentate LTP could be reversed by a subsequent low-frequency stimulation. This depotentiation was also attenuated by either OFQ or D-AP5 applied during low-frequency stimulation. These results, together with our previous findings, suggest that OFQ inhibits bidirectional changes in synaptic strength in the dentate; and its multiple actions on NMDA receptor-dependent, long-term synaptic plasticity might work in tandem to regulate hippocampus-dependent learning and memory.

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“…Classical opioid ligands do not bind to ORL1, but orphanin FQ͞nociceptin (OFQ͞N), a 17-amino acid neuropeptide purified from brain extracts, was found to be the natural ligand of the G protein-coupled receptor ORL1 (3,4). OFQ͞N, its precursor peptide, and its receptor ORL1 are located in corticolimbic regions involved in the integration of the emotional components of fear and stress as well as in the spinal cord, with a pattern distinct from that of opioid peptides and receptors in rodents (5)(6)(7)(8)(9). The expression of OFQ͞N or its receptor in the amygdaloid complex, septohippocampal region, periaqueductal gray matter, locus coeruleus, and dorsal raphe nucleus suggests that major brain neuronal systems may be sensitive to the action of OFQ͞N.…”

mentioning

confidence: 99%

A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: Anxiolytic profile in the rat

Jenck

Wichmann²,

Dautzenberg³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

263

249

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The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound {(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one} has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg͞kg i.p.). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (>10 mg͞kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ͞nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ͞nociceptin in adaptive behavioral fear responses to stress.T he ORL1 orphan receptor was identified from a human cDNA library on the basis of close homology (Ϸ65% in the transmembrane domains) with the -, ␦-, and -opioid receptors (1, 2). Classical opioid ligands do not bind to ORL1, but orphanin FQ͞nociceptin (OFQ͞N), a 17-amino acid neuropeptide purified from brain extracts, was found to be the natural ligand of the G protein-coupled receptor ORL1 (3, 4). OFQ͞N, its precursor peptide, and its receptor ORL1 are located in corticolimbic regions involved in the integration of the emotional components of fear and stress as well as in the spinal cord, with a pattern distinct from that of opioid peptides and receptors in rodents (5-9). The expression of OFQ͞N or its receptor in the amygdaloid complex, septohippocampal region, periaqueductal gray matter, locus coeruleus, and dorsal raphe nucleus suggests that major brain neuronal systems may be sensitive to the action of OFQ͞N. Such sensitivity has widespread implications for many aspects of behavior including arousal, attention, neuroendocrine control, fear, and anxiety (10). In brain slices, OFQ͞N has potent inhibitory actions on neurons in the dorsal raphe nucleus, the locus coeruleus, the periaqueductal gray matter, and the amygdala (11)(12)(13)(14). In general, OFQ͞N plays an inhibitory role on synaptic transmission in the central nervous system and thereby may contribute to a reduction in responsiveness to stress. When given intracerebroventricularly to rodents, OFQ͞N reduces elementary stress-induced physiological respon...

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Autoradiographic localization of [3H]nociceptin binding sites from telencephalic to mesencephalic regions of the mouse brain

Cited by 52 publications

References 20 publications

[ 3 H]ac-RYYRWK-NH 2 , a novel specific radioligand for the nociceptin/orphanin FQ receptor

[ 3 H]ac-RYYRWK-NH 2 , a novel specific radioligand for the nociceptin/orphanin FQ receptor

Orphanin FQ Suppresses NMDA Receptor-Dependent Long-Term Depression and Depotentiation in Hippocampal Dentate Gyrus

A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: Anxiolytic profile in the rat

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