In vitro pharmacological profile of peptide III-BTD - A novel ligand for nociceptin/orphanin FQ and opioid receptors

摘要

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 (pEC(50) 5.91 and 6.18, respectively; E-max 94 +/- 1% and 94 +/- 2%) and this effect was blocked by naloxone (1 muM). 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 muM). In the presence of 1 muM naloxone, 1 muM III-BTD shifted to the right the concentration response curve of nociceptin in a parallel manner, showing pK(B) 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 [S-35]GTP gammaS binding assay performed on cells expressing the recombinant human receptors. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 23]