Further studies on the pharmacological features of the nociceptin/orphanin FQ receptor ligand ZP120

• Published in: Peptides (New York, N.Y. : 1980) Vol. 30; no. 2; pp. 248 - 255
• Main Authors: Fischetti, Carmela, Rizzi, Anna, Gavioli, Elaine C., Marzola, Giuliano, Trapella, Claudio, Guerrini, Remo, Petersen, Jorgen S., Calo, Girolamo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2009; Elsevier
• Subjects: Animals; Biological and medical sciences; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Ligands; Male; Mice; Mice, Knockout; Motor Activity; Mouse and rat vas deferens; Narcotic Antagonists; Nociceptin; Nociceptin/orphanin FQ; NOP receptor; Oligopeptides - pharmacology; Opioid Peptides - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid - genetics; Receptors, Opioid - metabolism; Tail-withdrawal assay; Vas Deferens - drug effects; Vasodilator Agents - pharmacology; Vertebrates: endocrinology; ZP120; ZP120; Nociceptin/orphanin FQ; Mouse and rat vas deferens; Tail-withdrawal assay; NOP receptor; Semen pathway; Rat; Ligand; Rodentia; Male genital duct; Male genital system; Vas deferens; Assay; Nociceptin; Vertebrata; Mammalia; Mouse; N/OFQ receptor; Animal; Tail
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2008.10.001

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 p K B values (≈7.8). UFP-101 antagonized the actions of N/OFQ (p K B values ≈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.