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In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor.
Peptides 2007; 28(6):1240-51P

Abstract

[(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112) has been designed as a novel ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) by combining into the same peptide different chemical modifications reported to increase N/OFQ potency. In vitro data obtained in the electrically stimulated mouse vas deferens demonstrated that UFP-112 behaved as a high potency (pEC(50) 9.43) full agonist at the NOP receptor. UFP-112 effects were sensitive to the NOP antagonist UFP-101 but not to naloxone and no longer evident in tissues taken from NOP(-/-) mice. In vitro half life of UFP-112 in mouse plasma and brain homogenate was 2.6- and 3.5-fold higher than that of N/OFQ. In vivo, in the mouse tail withdrawal assay, UFP-112 (1-100pmol, i.c.v.) mimicked the actions of N/OFQ producing pronociceptive effects after i.c.v. administration and antinociceptive effects when given i.t.; in both cases, UFP-112 was approximately 100-fold more potent than the natural peptide and produced longer lasting effects. UFP-112 also mimicked the hyperphagic effect of N/OFQ producing a bell shaped dose response curve with the maximum reached at 10pmol. The hyperphagic effects of N/OFQ and UFP-112 were absent in NOP(-/-) mice. Equi-effective high doses of UFP-112 (0.1nmol) and N/OFQ (10nmol) were injected i.c.v. in mice and spontaneous locomotor activity recorded for 16h. N/OFQ produced a clear inhibitory effect which lasted for 60min while UFP-112 elicited longer lasting effects (>6h). In conscious rats, UFP-112 (0.1 and 10nmol/kg, i.v.) produced a marked and sustained decrease in heart rate, blood pressure, and urinary sodium excretion and a profound increase in urine flow. Collectively, these findings demonstrate that UFP-112 behaves in vitro and in vivo as a highly potent and selective ligand able to produce full and long lasting activation of NOP receptors.

Authors+Show Affiliations

Department of Experimental and Clinical Medicine, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Via Fossato di Mortara 17, 44100 Ferrara, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17532097

Citation

Rizzi, Anna, et al. "In Vitro and in Vivo Studies On UFP-112, a Novel Potent and Long Lasting Agonist Selective for the Nociceptin/orphanin FQ Receptor." Peptides, vol. 28, no. 6, 2007, pp. 1240-51.
Rizzi A, Spagnolo B, Wainford RD, et al. In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor. Peptides. 2007;28(6):1240-51.
Rizzi, A., Spagnolo, B., Wainford, R. D., Fischetti, C., Guerrini, R., Marzola, G., ... Calo, G. (2007). In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor. Peptides, 28(6), pp. 1240-51.
Rizzi A, et al. In Vitro and in Vivo Studies On UFP-112, a Novel Potent and Long Lasting Agonist Selective for the Nociceptin/orphanin FQ Receptor. Peptides. 2007;28(6):1240-51. PubMed PMID: 17532097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor. AU - Rizzi,Anna, AU - Spagnolo,Barbara, AU - Wainford,Richard D, AU - Fischetti,Carmela, AU - Guerrini,Remo, AU - Marzola,Giuliano, AU - Baldisserotto,Anna, AU - Salvadori,Severo, AU - Regoli,Domenico, AU - Kapusta,Daniel R, AU - Calo,Girolamo, Y1 - 2007/05/06/ PY - 2007/03/06/received PY - 2007/04/27/revised PY - 2007/04/30/accepted PY - 2007/5/29/pubmed PY - 2007/9/6/medline PY - 2007/5/29/entrez SP - 1240 EP - 51 JF - Peptides JO - Peptides VL - 28 IS - 6 N2 - [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112) has been designed as a novel ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) by combining into the same peptide different chemical modifications reported to increase N/OFQ potency. In vitro data obtained in the electrically stimulated mouse vas deferens demonstrated that UFP-112 behaved as a high potency (pEC(50) 9.43) full agonist at the NOP receptor. UFP-112 effects were sensitive to the NOP antagonist UFP-101 but not to naloxone and no longer evident in tissues taken from NOP(-/-) mice. In vitro half life of UFP-112 in mouse plasma and brain homogenate was 2.6- and 3.5-fold higher than that of N/OFQ. In vivo, in the mouse tail withdrawal assay, UFP-112 (1-100pmol, i.c.v.) mimicked the actions of N/OFQ producing pronociceptive effects after i.c.v. administration and antinociceptive effects when given i.t.; in both cases, UFP-112 was approximately 100-fold more potent than the natural peptide and produced longer lasting effects. UFP-112 also mimicked the hyperphagic effect of N/OFQ producing a bell shaped dose response curve with the maximum reached at 10pmol. The hyperphagic effects of N/OFQ and UFP-112 were absent in NOP(-/-) mice. Equi-effective high doses of UFP-112 (0.1nmol) and N/OFQ (10nmol) were injected i.c.v. in mice and spontaneous locomotor activity recorded for 16h. N/OFQ produced a clear inhibitory effect which lasted for 60min while UFP-112 elicited longer lasting effects (>6h). In conscious rats, UFP-112 (0.1 and 10nmol/kg, i.v.) produced a marked and sustained decrease in heart rate, blood pressure, and urinary sodium excretion and a profound increase in urine flow. Collectively, these findings demonstrate that UFP-112 behaves in vitro and in vivo as a highly potent and selective ligand able to produce full and long lasting activation of NOP receptors. SN - 0196-9781 UR - https://www.unboundmedicine.com/medline/citation/17532097/In_vitro_and_in_vivo_studies_on_UFP_112_a_novel_potent_and_long_lasting_agonist_selective_for_the_nociceptin/orphanin_FQ_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(07)00161-1 DB - PRIME DP - Unbound Medicine ER -