title: Further studies on the pharmacological features of the nociceptin/orphanin FQ receptor ligand ZP120.
abstract: ZP120 is a nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) ligand. In previous studies, the effects of ZP120 were found to be sensitive to J-113397 in mouse tissues while resistant to UFP-101 in rat tissues. The aim of this study was to further investigate the ZP120 pharmacological profile using mouse and rat preparations, J-113397 and UFP-101, as well as NOP receptor knockout (NOP(-/-)) mice. Electrically stimulated mouse and rat vas deferens were used to characterize the pharmacology of ZP120 in vitro. For in vivo studies the tail-withdrawal assay was performed in wild type (NOP(+/+)) and NOP knockout (NOP(-/-)) mice. In the mouse and rat vas deferens ZP120 mimicked the effects of N/OFQ showing higher potency but lower maximal effects. In both preparations, J-113397 antagonized N/OFQ and ZP120 effects showing similar pK(B) values ( approximately 7.8). UFP-101 antagonized the actions of N/OFQ (pK(B) values approximately 7.3) but did not modify the effects of ZP120. The inhibitory effects of N/OFQ and ZP120 were no longer evident in vas deferens tissues taken from NOP(-/-) mice. In NOP(+/+) mice subjected to the tail-withdrawal assay, ZP120 (1 nmol) mimicked the pronociceptive action of N/OFQ (10 nmol), producing longer lasting effects. The effects of both peptides were absent in NOP(-/-) animals. The NOP receptor ligand ZP120 is a high potency NOP selective partial agonist able to evoke long-lasting effects; its diverse antagonist sensitivity in comparison with N/OFQ may derive from different modality of binding to the NOP receptor.
authors.affiliation: Department Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, University of Ferrara, and National Institute of Neuroscience, Ferrara, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fischetti
authors.forename: Anna
authors.initials: A
authors.lastname: Rizzi
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Marzola
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Jorgen S
authors.initials: JS
authors.lastname: Petersen
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D008024:Ligands; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000097629:Nociceptin; C473470:ZP120