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

Abstract

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.

• Authors: Rumi Naono, Tomohiro Nakayama, Tetsuya Ikeda, Osamu Matsushima, Toshikazu Nishimori
• Journal: Brain research (Brain Res) Vol. 1165 Pg. 71-80 (Aug 24 2007) ISSN: 0006-8993 [Print] Netherlands
• PMID: 17655832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Protein Precursors
• Proto-Oncogene Proteins c-fos
• Tachykinins
• preprotachykinin
• Substance P
• Hexokinase
• Leucine

Topics

• Animals
• Behavior, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Hexokinase
• Hyperalgesia (chemically induced, prevention & control)
• Leucine (metabolism)
• Male
• Pain (chemically induced, prevention & control)
• Pain Measurement (methods)
• Peptides (administration & dosage)
• Physical Stimulation
• Protein Precursors (chemistry, therapeutic use)
• Proto-Oncogene Proteins c-fos (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Spinal Cord (drug effects, metabolism)
• Substance P (antagonists & inhibitors)
• Tachykinins (chemistry, therapeutic use)