Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-9-18
pubmed:abstractText
The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is reported to be metabolized by aminopeptidase N and endopeptidase 24.15. In the present study, N/OFQ C-terminal fragments elicited nociceptive responses in the peripheral nociceptors and in the spinal cord, whereas N-terminal fragments had no significant nociception. The nociceptive effect of N/OFQ (13-17) was most potent and remained unchanged in N/OFQ peptide receptor (NOPR) gene knockout mice, indicating that N/OFQ (13-17)-induced nociception is mediated through a novel mechanism independent of the activation of NOPR. This finding was further confirmed by in vitro guanosine 5'-O-(3-[35S]thio)triphosphate binding experiments, in which N/OFQ (13-17) showed no significant binding activity in baculovirus/sf21 cells expressing NOPR together with G protein alpha(i)1-, beta1-, and gamma2-subunits, whereas N/OFQ showed stimulation in a concentration-dependent manner. On the other hand, although a typical bell-shaped dose-response relationship was observed with a wide range of N/OFQ doses in both peripheral and central nociception tests, N/OFQ (13-17) did not show bell-shaped dose-response relationship in the central nociception test. This finding indicates that N/OFQ (13-17), in contrast to N/OFQ, lacks the postsynaptic antinociceptive actions modulating substance P signaling in the spinal cord. Together, our results suggest that C-terminal fragments of N/OFQ have potent nociceptive actions, and N/OFQ (13-17) could have the potential to mediate its actions through a novel mechanism independent of the activation of NOPR in the nociceptors and in spinal synapses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Pronociceptive effects of nociceptin/orphanin FQ (13-17) at peripheral and spinal level in mice.
pubmed:affiliation
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Nagasaki, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't