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Quantitative study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP receptors in rat periaqueductal gray slices.
Eur J Pharmacol 2008; 579(1-3):110-5EJ

Abstract

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a novel member of the opioid receptor family with little affinity for traditional opioids. This receptor and its endogenous ligand, N/OFQ, are widely distributed in the brain and are implicated in many physiological functions including pain regulation. [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102) is a newly developed peptide agonist of NOP receptors. In this study, we quantitatively investigated the effect of UFP-102 at native NOP receptors of the ventrolateral periaqueductal gray (PAG), a crucial midbrain area involved in pain regulation and enriched with NOP receptors, using blind patch-clamp whole-cell recording technique in rat brain slices. UFP-102, like N/OFQ, induced an outward current in ventrolateral PAG neurons and increased the membrane current elicited by a hyperpolarization ramp from -60 to -140 mV. The current induced by UFP-102 was characterized with inward rectification and had a reversal potential near the equilibrium potential of K(+) ions, indicating that UFP-102 activates G-protein coupled inwardly rectifying K(+) channels. The effect of UFP-102 was concentration-dependent with the maximal effect similar to that of N/OFQ. The EC(50) value was 11+/-2 nM, which is 5 fold lower than that of N/OFQ. The effect of UFP-102 was not affected by naloxone while competitively antagonized by UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)), a potent NOP receptor antagonist, with a pA(2) value of 6.7. These results suggest that UFP-102 is a full agonist at the postsynaptic NOP receptors of the midbrain of rats and is 5 fold more potent than N/OFQ.

Authors+Show Affiliations

Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17976580

Citation

Kuo, Chia-Ju, et al. "Quantitative Study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP Receptors in Rat Periaqueductal Gray Slices." European Journal of Pharmacology, vol. 579, no. 1-3, 2008, pp. 110-5.
Kuo CJ, Liao YY, Guerrini R, et al. Quantitative study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP receptors in rat periaqueductal gray slices. Eur J Pharmacol. 2008;579(1-3):110-5.
Kuo, C. J., Liao, Y. Y., Guerrini, R., Calo', G., & Chiou, L. C. (2008). Quantitative study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP receptors in rat periaqueductal gray slices. European Journal of Pharmacology, 579(1-3), pp. 110-5.
Kuo CJ, et al. Quantitative Study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP Receptors in Rat Periaqueductal Gray Slices. Eur J Pharmacol. 2008 Jan 28;579(1-3):110-5. PubMed PMID: 17976580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative study of [(pF)Phe4,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-102) at NOP receptors in rat periaqueductal gray slices. AU - Kuo,Chia-Ju, AU - Liao,Yan-Yu, AU - Guerrini,Remo, AU - Calo',Girolamo, AU - Chiou,Lih-Chu, Y1 - 2007/10/11/ PY - 2007/05/20/received PY - 2007/10/02/revised PY - 2007/10/04/accepted PY - 2007/11/3/pubmed PY - 2008/4/16/medline PY - 2007/11/3/entrez SP - 110 EP - 5 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 579 IS - 1-3 N2 - The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a novel member of the opioid receptor family with little affinity for traditional opioids. This receptor and its endogenous ligand, N/OFQ, are widely distributed in the brain and are implicated in many physiological functions including pain regulation. [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102) is a newly developed peptide agonist of NOP receptors. In this study, we quantitatively investigated the effect of UFP-102 at native NOP receptors of the ventrolateral periaqueductal gray (PAG), a crucial midbrain area involved in pain regulation and enriched with NOP receptors, using blind patch-clamp whole-cell recording technique in rat brain slices. UFP-102, like N/OFQ, induced an outward current in ventrolateral PAG neurons and increased the membrane current elicited by a hyperpolarization ramp from -60 to -140 mV. The current induced by UFP-102 was characterized with inward rectification and had a reversal potential near the equilibrium potential of K(+) ions, indicating that UFP-102 activates G-protein coupled inwardly rectifying K(+) channels. The effect of UFP-102 was concentration-dependent with the maximal effect similar to that of N/OFQ. The EC(50) value was 11+/-2 nM, which is 5 fold lower than that of N/OFQ. The effect of UFP-102 was not affected by naloxone while competitively antagonized by UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)), a potent NOP receptor antagonist, with a pA(2) value of 6.7. These results suggest that UFP-102 is a full agonist at the postsynaptic NOP receptors of the midbrain of rats and is 5 fold more potent than N/OFQ. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17976580/Quantitative_study_of_[_pF_Phe4Arg14Lys15]nociceptin/orphanin_FQ_NH2__UFP_102__at_NOP_receptors_in_rat_periaqueductal_gray_slices_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)01107-7 DB - PRIME DP - Unbound Medicine ER -