Study in vitro and in vivo of nociceptin/orphanin FQ(1-13)NH2 analogues substituting N-Me-Gly for Gly2 or Gly3.
Abstract
In the present study, two analogues containing N-Me-Gly (Sarcosine, Sar) were synthesized
to further investigate the structural-activity relationships of orphanin FQ/nociceptin
(OFQ/NC, NC). The replacement of Gly(2) or Gly(3) with Sar increased the flexibility
and decreased the hydrophobicity of the N-terminal tetrapeptide. The activity of the
analogues was investigated in a series of assays in vivo and in vitro. [Sar(2)]NC(1-13)NH(2)
was found to (1) produce dose-dependent inhibition of the electrically induced contraction
in MVD assay (pEC(50) = 6.14); (2) produce significant hyperalgesia effects in a dose-dependent
manner when intracerebroventricularly (i.c.v.) injected in mice. The inhibitive effects
of [Sar(2)]NC(1-13)NH(2) in MVD assay could be significantly antagonized by [Nphe(1)]NC(1-13)NH(2),
and partially antagonized by naloxone; the hyperalgesic effect of [Sar(2)]NC(1-13)NH(2)
could be significantly antagonized by naloxone, and partially antagonized by [Nphe(1)]NC(1-13)NH(2).
On the contrary, [Sar(3)]NC(1-13)NH(2) showed no effects in these assays. All the
findings suggest that the flexibility of the peptide bond between Phe(1) and Gly(2)
and between Gly(2) and Gly(3) play an important role in NC-OP(4) receptor interaction,
and the hydrophobicity of the N-terminal tetrapeptide showed no significant effect
on this interaction. The present work also helps to provide a novel method to elucidate
structural and conformational requirements of the opioid peptide-receptor interaction.
Type
Journal articleSubject
Amino Acid SubstitutionAnimals
Glycine
Male
Mice
Oligopeptides
Opioid Peptides
Pain Measurement
Sarcosine
Structure-Activity Relationship
Vas Deferens
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https://hdl.handle.net/10161/13664Published Version (Please cite this version)
10.1016/j.peptides.2004.05.012Publication Info
Chen, Li-xiang; Fang, Quan; Chen, Qiang; Guo, Jia; Wang, Zhuan-zi; Chen, Yong; & Wang,
Rui (2004). Study in vitro and in vivo of nociceptin/orphanin FQ(1-13)NH2 analogues substituting
N-Me-Gly for Gly2 or Gly3. Peptides, 25(8). pp. 1349-1354. 10.1016/j.peptides.2004.05.012. Retrieved from https://hdl.handle.net/10161/13664.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yong Chen
Associate Professor in Neurology

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