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NPYF a, A Chimeric Peptide of Met‐Enkephalin, and NPFF Induces Tolerance‐Free Analgesia
Ist Teil von
Chemical biology & drug design, 2016-06, Vol.87 (6), p.885-894
Erscheinungsjahr
2016
Quelle
Wiley Online Library
Beschreibungen/Notizen
Methionine‐enkephalin‐Arg‐Phe is an endogenous amphiactive analgesic peptide. Neuropeptide FF, on the other hand, is reported for its role in opioid modulation and tolerance development. Based on these reports, in the present study we designed a chimeric peptide
NPYF
a (
YGGFMKKKPQRF
amide), having the Met‐enkephalin (opioid) and
PQRF
amide sequence of neuropeptide FF, which can then target both the opioid and neuropeptide FF receptors. We hypothesized that the chimeric peptide so designed would have both analgesic properties and further aid in understanding of the role of neuropeptide FF in the development of opiate tolerance. Our studies indicated that
NPYF
a induced an early onset, potent, dose‐dependent and prolonged antinociception. Additionally, antagonists (
MOR
,
KOR
, and
DOR
) pretreatment studies determined a
KOR
‐mediated antinociception activity of the ligand. Further,
in vitro
binding studies using the Eu‐
GTP
‐
γ
S binding assay on cell lines expressing opioid and
NPFF
receptors showed binding to both the opioid and neuropeptide FF receptors suggesting a multiple receptor binding character of
NPYF
a. Moreover, chronic (6 days) treatment with
NPYF
a exhibited an absence of tolerance development subsequent to its analgesia. The current study proposes
NPYF
a as a potent, long‐acting antinociceptor lacking tolerance development as well as a probe to study opioid analgesia and the associated complex mechanisms of tolerance development.
Sprache
Englisch
Identifikatoren
ISSN: 1747-0277
eISSN: 1747-0285
DOI: 10.1111/cbdd.12721
Titel-ID: cdi_crossref_primary_10_1111_cbdd_12721
Format
–
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