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Raffaella Vergura

Bio: Raffaella Vergura is an academic researcher from University of Ferrara. The author has contributed to research in topics: Agonist & Receptor. The author has an hindex of 7, co-authored 9 publications receiving 458 citations.

Papers
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Journal ArticleDOI
TL;DR: The effects of in vivo supraspinal NPS in mice are evaluated and it is shown that in vivo NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic‐like effects.
Abstract: Background and purpose: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice. Experimental approach: Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice. Key results: NPS (0.01–1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5 mg kg−1). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15 mg kg−1) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively. Conclusions and implications: We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders. British Journal of Pharmacology (2008) 154, 471–479; doi:10.1038/bjp.2008.96; published online 31 March 2008

175 citations

Journal ArticleDOI
TL;DR: This study identified the amino acid residues of this peptide most important for receptor activation as Thr8-Gly9-Met10, suggesting that the C-terminal region of the peptide maintains importance for in vivo activity.

93 citations

Journal ArticleDOI
01 Jan 2008-Peptides
TL;DR: The present findings demonstrate that UFP-512 behaves as a highly potent and selective agonist at Dop receptors and corroborate the proposal that the selective activation of DOP receptors elicits robust anxiolytic- and antidepressant-like effects in rodents.

83 citations

Journal ArticleDOI
01 Aug 2005-Peptides
TL;DR: It is demonstrated that N/OFQ stimulates human monocyte chemotaxis via NOP receptor activation through the order of potency of agonists and the antagonist selectivity.

45 citations

Journal ArticleDOI
TL;DR: UFP‐803 is a potent UT receptor ligand which displays competitive/noncompetitive antagonist behavior depending on the assay, and is less potent than urantide, which displayed reduced residual agonist activity and as such may be a useful pharmacological tool.
Abstract: The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to the right, revealing a competitive type of antagonism and a pA(2) value of 7.46. In the FLIPR [Ca(2+)](i) assay, performed at room temperature in HEK293(hUT) and HEK293(rUT) cells, U-II increased [Ca(2+)](i) with pEC(50) values of 8.11 and 8.48. Urantide and UFP-803 were inactive as agonists, but antagonized the actions of U-II by reducing, in a concentration-dependent manner, the agonist maximal effects with apparent pK(B) values in the range of 8.45-9.05. In a separate series of experiments performed at 37 degrees C using a cuvette-based [Ca(2+)](i) assay and CHO(hUT) cells, urantide mimicked the [Ca(2+)](i) stimulatory effect of U-II with an intrinsic activity (alpha) of 0.80, while UFP-803 displayed a small (alpha=0.21) but consistent residual agonist activity. When the same experiments were repeated at 22 degrees C (a temperature similar to that in FLIPR experiments), urantide displayed a very small intrinsic activity (alpha=0.11) and UFP-803 was completely inactive as an agonist. In vivo in mice, UFP-803 (10 nmol kg(-1)) antagonized U-II (1 nmol kg(-1))-induced increase in plasma extravasation in various vascular beds, while being inactive alone. In conclusion, UFP-803 is a potent UT receptor ligand which displays competitive/noncompetitive antagonist behavior depending on the assay. While UFP-803 is less potent than urantide, it displayed reduced residual agonist activity and as such may be a useful pharmacological tool.

34 citations


Cited by
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Journal ArticleDOI
TL;DR: To date, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address DOR and KOR function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment, and social behaviors.

425 citations

Journal ArticleDOI
TL;DR: The N/OFQ-NOP system has been implicated in a wide range of biological functions, including pain, drug abuse, cardiovascular control and immunity as mentioned in this paper, and the current status of the very limited number of clinical trials.
Abstract: Identification of the enigmatic nociceptin/orphanin FQ peptide (N/OFQ) in 1995 represented the first successful use of reverse pharmacology and led to deorphanization of the N/OFQ receptor (NOP). Subsequently, the N/OFQ-NOP system has been implicated in a wide range of biological functions, including pain, drug abuse, cardiovascular control and immunity. Although this could be considered a hurdle for the development of pharmaceuticals selective for a specific disease indication, NOP represents a viable drug target. This article describes potential clinical indications and highlights the current status of the very limited number of clinical trials.

331 citations

Journal ArticleDOI
TL;DR: The recent demonstration of biased agonism at the delta opioid receptor in vivo opens novel perspectives towards targeting specific therapeutic effects through drug design.

261 citations

Journal ArticleDOI
TL;DR: 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 is discussed.
Abstract: 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.

224 citations

Journal ArticleDOI
TL;DR: The effects of in vivo supraspinal NPS in mice are evaluated and it is shown that in vivo NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic‐like effects.
Abstract: Background and purpose: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice. Experimental approach: Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice. Key results: NPS (0.01–1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5 mg kg−1). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15 mg kg−1) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively. Conclusions and implications: We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders. British Journal of Pharmacology (2008) 154, 471–479; doi:10.1038/bjp.2008.96; published online 31 March 2008

175 citations