[Nphe1,Arg14,Lys15]N/OFQ-NH2 is a competitive antagonist of NOP receptors in the periaqueductal gray.

Abstract

Nociceptin/orphanin FQ (N/OFQ) and N/OFQ peptide (NOP) receptors are implicated in many physiological functions including pain regulation. This study quantitatively investigated the interaction of a novel NOP receptor antagonist, UFP-101 ([Nphe1,Arg14,Lys15]N/OFQ-NH2), with N/OFQ in the ventrolateral periaqueductal gray, a crucial midbrain area for pain regulation. N/OFQ concentration-dependently activated G-protein coupled inwardly rectifying K+ (GIRK) channels in ventrolateral neurons of periaqueductal gray slices. UFP-101 antagonized N/OFQ-induced GIRK channel activation in a concentration-dependent manner and produced a parallel shift of the concentration-response curve of N/OFQ. The pA2 value estimated from Schild plot is 6.92+/-0.06. At concentrations up to 1 microM, UFP-101 had no effect on membrane current per se and did not affect the GIRK current activated by [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin, a mu-opioid receptor agonist. It is concluded that UFP-101 is a potent and competitive peptide antagonist of NOP receptors that mediate GIRK channel activation in ventrolateral periaqueductal gray neurons.

• Authors: Lih-Chu Chiou, Yan-Yu Liao, Remo Guerrini, Girolamo Calo'
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 515 Issue 1-3 Pg. 47-53 (May 16 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15896734 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)
• Narcotic Antagonists
• Opioid Peptides
• Potassium Channels, Inwardly Rectifying
• Receptors, Opioid
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• nociceptin

Topics

• Animals
• Binding, Competitive (drug effects)
• Dose-Response Relationship, Drug
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)- (pharmacology)
• In Vitro Techniques
• Membrane Potentials (drug effects)
• Narcotic Antagonists
• Neurons (drug effects, physiology)
• Opioid Peptides (metabolism, pharmacology)
• Periaqueductal Gray (drug effects, metabolism)
• Potassium Channels, Inwardly Rectifying (physiology)
• Rats
• Rats, Wistar
• Receptors, Opioid (metabolism)