title: [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.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Rd., Section 1, Taipei 100, Taiwan. lcchiou@ha.mc.ntu.edu.tw
authors.forename: Lih-Chu
authors.initials: LC
authors.lastname: Chiou
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Liao
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009292:Narcotic Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D000097629:Nociceptin
chemical_list: D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D024661:Potassium Channels, Inwardly Rectifying; D011957:Receptors, Opioid; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)