title: In vitro pharmacological profile of peptide III-BTD: a novel ligand for nociceptin/orphanin FQ and opioid receptors.
abstract: Peptide III-BTD has been recently identified as a non-selective nociceptin/orphanin FQ receptor ligand by screening of a synthetic peptide combinatorial library. In the present study we evaluated the pharmacological profile of peptide III-BTD in isolated tissues (mouse and rat vas deferens, guinea pig ileum) sensitive to both nociceptin and opioid peptides. In the mouse vas deferens and guinea pig ileum, III-BTD concentration dependently inhibited the electrically induced twitch (pEC50 5.91 and 6.18, respectively; Emax 94 +/- 1% and 94 +/- 2%) and this effect was blocked by naloxone (1 microM). In the rat vas deferens, III-BTD was inactive in most of the tissues, while in few others it elicited a slight inhibition only at the highest concentration tested (10 microM). In the presence of 1 microM naloxone, 1 microM III-BTD shifted to the right the concentration response curve of nociceptin in a parallel manner, showing pKB values in the range 6.6-6.9. These data confirm on native nociceptin receptors the pharmacological profile of peptide III-BTD which behaved as a mixed nociceptin receptor antagonist/opioid receptor agonist in the [35S]GTPyS binding assay performed on cells expressing the recombinant human receptors.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bigoni
authors.forename: A
authors.initials: A
authors.lastname: Rizzi
authors.forename: D
authors.initials: D
authors.lastname: Rizzi
authors.forename: J A
authors.initials: JA
authors.lastname: Becker
authors.forename: B L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: F
authors.initials: F
authors.lastname: Simonin
authors.forename: D
authors.initials: D
authors.lastname: Regoli
authors.forename: G
authors.initials: G
authors.lastname: Calo
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D019151:Peptide Library; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008024:Ligands; D009270:Naloxone; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D019151:Peptide Library; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin