Pharmacological profile of NOP receptors coupled with calcium signaling via the chimeric protein Gαqi5

Camarda, Valeria; Fischetti, Carmela; Anzellotti, Nicholas; Molinari, Paola; Ambrosio, Caterina; Kostenis, Evi; Regoli, Doménico; Trapella, Claudio; Guerrini, Remo; Salvadori, Severo; Calò, Girolamo

doi:10.1007/s00210-009-0396-x

Cited by 60 publications

(71 citation statements)

References 39 publications

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“…This basic in vitro pharmacological profile has been confirmed in several studies using different assays (Dautzenberg et al, 2001;Hashiba et al, 2002;McDonald et al, 2003a;McLeod et al, 2004;Camarda et al, 2009 (Gehlert et al, 2006). However, other results underlined some differences in Ro 64-6198 versus N/OFQ in vitro actions.…”

Section: B Nociceptin/orphanin Fq Unrelated Peptidesmentioning

confidence: 56%

“…Each of these compounds is characterized by a slow kinetics of activation of the NOP receptor, as suggested by bioassay experiments in isolated tissues (Rizzi et al, 2002c;Calo' et al, 2011;Guerrini et al, 2014). It is possible that the rapid kinetics that characterize the calcium transient response may be incompatible with the slow kinetics of the ligand receptor interaction (for a detailed discussion of this topic see Camarda et al, 2009;Rizzi et al, 2014). In vivo, however, ZP120 displayed very high potency and long duration of action in locomotor activity and tail withdrawal experiments in mice , effects that were no longer present in NOP(2/2) mice (Fischetti et al, 2009a).…”

Section: B Nociceptin/orphanin Fq Unrelated Peptidesmentioning

confidence: 99%

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Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor

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Section: B Nociceptin/orphanin Fq Unrelated Peptidesmentioning

confidence: 56%

Section: B Nociceptin/orphanin Fq Unrelated Peptidesmentioning

confidence: 99%

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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“…The spinal antinociceptive action of the NOP partial agonist UFP-113 (Arduin et al, 2007;Camarda et al, 2009) has been evaluated in the present research for the first time. Acute i.t.…”

Section: Discussionmentioning

confidence: 99%

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Micheli

Mannelli

Guerrini

et al. 2015

European Journal of Pharmacology

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a b s t r a c tSevere pain occurs in the context of many diseases and conditions and is a leading cause of disability. Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ peptide (NOP) receptor. This peptidergic system controls pain transmission and in particular spinally administered N/OFQ has robust antinociceptive properties.The aim of this study was to investigate the spinal antinociceptive properties of NOP peptide agonists after acute and subchronic treatment in rats. Doses unable to alter motor coordination were selected. UFP-112 (full NOP agonist) and UFP-113 (partial NOP agonist) were administered intrathecally (i.t.) by spinal catheterization. Acute injection of UFP-112 induced antinociceptive response at lower dosages (0.03-1 nmol i.t.) compared to morphine and similar to N/OFQ. UFP-113 was effective in a 0.001-1 nmol i.t. dose range. The antinociceptive effects of NOP ligands were no longer evident in rats knockout for the NOP gene, while those of morphine were maintained. The continuous spinal infusion (by osmotic pumps) of 0.1 nmol/h UFP-112 and UFP-113 showed antinociceptive action comparable to 1-3 nmol/h morphine or N/OFQ. The antinociceptive effect of morphine progressively decreased and was no longer significant after 6 days of treatment. Similar results were obtained with N/OFQ, UFP-112, and UFP-113. The acute i.t. injection of morphine in animals tolerant to N/OFQ and UFP-112 evoked analgesic effects. Neither morphine nor N/OFQ induced antinociceptive effects in morphine-and UFP-113-tolerant rats. In conclusion this study highlights the analgesic efficacy and potency of UFP-112 and UFP-113 underlining the relevance of NOP system in analgesia.

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“…CHO cells stably coexpressing either human recombinant NOP, mu or kappa receptor along with the C-terminally modified Gα qi5 chimeric protein and cells co-expressing the delta receptor and the Gα qG66Di5 chimeric protein were generated as previously described (Camarda and Calo, 2013; Camarda et al, 2009). Cells were cultured in culture medium consisting of Dulbecco’s modified Eagle’s medium (DMEM)/HAMS F12 (1:1) supplemented with 10% fetal bovine serum (FBS), penicillin (100 IU/ml), streptomycin (100 μg/ml), L-glutamine (2 mM); fungizone (1 μg/ml), geneticin (G418; 200 μg/ml) and hygromycin B (100 μg/ml).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological studies on the NOP and opioid receptor agonist PWT2-[Dmt1]N/OFQ(1-13)

Cerlesi

Ding

Bird

et al. 2017

European Journal of Pharmacology

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An innovative chemical strategy named peptide welding technology (PWT) has been developed for the facile synthesis of tetrabranched peptides. [Dmt1]N/OFQ(1-13)-NH2 acts as a universal agonist for nociceptin/orphanin FQ (N/OFQ) and classical opioid receptors. The present study investigated the pharmacological profile of the PWT derivative of [Dmt1]N/OFQ(1-13)NH2 (PWT2-[Dmt1]) in several assays in vitro and in vivo after spinal administration in monkeys subjected to the tail withdrawal assay. PWT2-[Dmt1] mimicked the effects of [Dmt1]N/OFQ(1-13)-NH2 displaying full agonist activity, similar affinity/potency and selectivity at human recombinant N/OFQ (NOP) and opioid receptors in receptor binding, stimulation of [35S]GTPγS binding, calcium mobilization in cells expressing chimeric G proteins, and BRET studies for measuring receptor/G-protein and receptor/β-arrestin 2 interaction. In vivo in monkeys PWT2-[Dmt1] elicited dose-dependent and robust antinociceptive effects being more potent and longer lasting than [Dmt1]N/OFQ(1-13)-NH2. The analgesic action of PWT2-[Dmt1] was sensitive to the NOP receptor antagonist J-113397, but not naltrexone. Thus, the present study demonstrated that the tetrabranched derivative of [Dmt1]N/OFQ(1-13)-NH2 obtained with the PWT technology maintains the in vitro pharmacological profile of the parent peptide but displays higher potency and longer lasting action in vivo.

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Pharmacological profile of NOP receptors coupled with calcium signaling via the chimeric protein Gαqi5

Cited by 60 publications

References 39 publications

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Pharmacological studies on the NOP and opioid receptor agonist PWT2-[Dmt1]N/OFQ(1-13)

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