RGD Reference Report - Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing. - Rat Genome Database

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Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing.

Authors: Naono, Rumi  Nakayama, Tomohiro  Ikeda, Tetsuya  Matsushima, Osamu  Nishimori, Toshikazu 
Citation: Naono R, etal., Brain Res. 2007 Aug 24;1165:71-80. doi: 10.1016/j.brainres.2007.05.062. Epub 2007 Jul 3.
RGD ID: 14695074
Pubmed: PMID:17655832   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2007.05.062   (Journal Full-text)

Endokinins are tachykinin peptides designated from a human preprotachykinin C (PPT-C, TAC4) gene and consist of endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). A representative of mammalian tachykinins is substance P (SP), which functions as a neurotransmitter or modulator in the pain system; however, little is known about the role of these endokinins, especially EKC and EKD, in pain processing. Therefore, we evaluated the effects of EKC/D (using the common carboxyl-terminal duodecapeptide in EKC and EKD) on pain processing in rats. Pretreatment with EKC/D prevented induction of scratching behavior and thermal hyperalgesia by intrathecal administration of EKA/B (using the common C-terminal decapeptide in EKA and EKB) and SP and c-Fos expression in laminae I/II and V/VI of the spinal cord by noxious thermal stimulation. A prominent difference between EKC/D and SP is the presence of leucine instead of methionine at the carboxyl-terminal of EKC/D. Thus, to clarify whether leucine at the carboxyl-terminal of EKC/D plays an important role in determining the inhibitory effect of this peptide, we intrathecally administered [Met(12)]-EKC/D in which only leucine of EKC/D is replaced by methionine. This peptide did not exhibit the inhibitory effect on SP-induced scratching behavior or thermal hyperalgesia but conversely caused thermal hyperalgesia. Taken together, these findings indicate that EKC/D has an inhibitory effect on pain processing in the rat spinal cord, and the effect is due to leucine at the carboxyl-terminal of EKC/D.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tac4Ratdetection of temperature stimulus involved in sensory perception of pain involved_inIDA PMID:17655832UniProt 
Tac4Ratpositive regulation of sensory perception of pain involved_inIDA PMID:17655832UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tac4Ratextracellular space located_inIDA PMID:17655832UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Tac4  (tachykinin precursor 4)


Additional Information