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The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats.
Neuroscience 2006; 141(4):2051-7N

Abstract

Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ-stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ-induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe(1),Arg(14),Lys(15)]nociceptin/orphanin FQ-NH(2) (UFP-101). We found that, at 30 min post-i.c.v. injection, N/OFQ dose-dependently increased plasma adrenocorticotrophin hormone and corticosterone compared with the vehicle-injected controls. N/OFQ (1.0 microg) significantly increased CRF mRNA but not AVP mRNA within the parvocellular hypothalamic paraventricular nucleus compared with the control group, and significantly increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. While UFP-101 (1.0 microg) alone had no significant effect on plasma corticosterone concentration it blocked the effect of N/OFQ (1.0 microg) on plasma corticosterone levels when compared with N/OFQ administered alone. UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ-induced HPA axis activation is mediated via central NOP receptors.

Authors+Show Affiliations

Department of Anatomy, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK. James.Leggett@bristol.ac.ukNo 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

16784820

Citation

Leggett, J D., et al. "The Nociceptin Receptor Antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 Blocks the Stimulatory Effects of Nociceptin/orphanin FQ On the HPA Axis in Rats." Neuroscience, vol. 141, no. 4, 2006, pp. 2051-7.
Leggett JD, Harbuz MS, Jessop DS, et al. The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats. Neuroscience. 2006;141(4):2051-7.
Leggett, J. D., Harbuz, M. S., Jessop, D. S., & Fulford, A. J. (2006). The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats. Neuroscience, 141(4), pp. 2051-7.
Leggett JD, et al. The Nociceptin Receptor Antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 Blocks the Stimulatory Effects of Nociceptin/orphanin FQ On the HPA Axis in Rats. Neuroscience. 2006 Sep 15;141(4):2051-7. PubMed PMID: 16784820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats. AU - Leggett,J D, AU - Harbuz,M S, AU - Jessop,D S, AU - Fulford,A J, Y1 - 2006/06/19/ PY - 2006/02/21/received PY - 2006/04/25/revised PY - 2006/05/17/accepted PY - 2006/6/21/pubmed PY - 2006/12/9/medline PY - 2006/6/21/entrez SP - 2051 EP - 7 JF - Neuroscience JO - Neuroscience VL - 141 IS - 4 N2 - Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ-stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ-induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe(1),Arg(14),Lys(15)]nociceptin/orphanin FQ-NH(2) (UFP-101). We found that, at 30 min post-i.c.v. injection, N/OFQ dose-dependently increased plasma adrenocorticotrophin hormone and corticosterone compared with the vehicle-injected controls. N/OFQ (1.0 microg) significantly increased CRF mRNA but not AVP mRNA within the parvocellular hypothalamic paraventricular nucleus compared with the control group, and significantly increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. While UFP-101 (1.0 microg) alone had no significant effect on plasma corticosterone concentration it blocked the effect of N/OFQ (1.0 microg) on plasma corticosterone levels when compared with N/OFQ administered alone. UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ-induced HPA axis activation is mediated via central NOP receptors. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16784820/The_nociceptin_receptor_antagonist_[Nphe1Arg14Lys15]nociceptin/orphanin_FQ_NH2_blocks_the_stimulatory_effects_of_nociceptin/orphanin_FQ_on_the_HPA_axis_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)00728-7 DB - PRIME DP - Unbound Medicine ER -