Effects of Endokinin A/B and Endokinin C/D on the modulation of pain in mice.
Endokinins are novel tachykinins encoded on the human TAC4 and consist of Endokinin A (EKA), B (EKB), C (EKC) and D (EKD). To date, the function of Endokinins in pain processing was not fully understood. Therefore the aim of this study was to investigate the effects of Endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) and Endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on pain modulation at supraspinal level in mice. Intracerebroventricular (i.c.v.) administration of EKA/B (1, 3, 12, 20nmol/mouse) dose dependently induced potent analgesic effect. This effect could be fully antagonized by SR140333B but not SR48968C or SR142801. Naloxone could also block the analgesic effect, suggesting that this analgesic effect is related to opioid receptors. However, i.c.v. administration of EKA/B (10, 30, 100pmol/mouse) caused hyperalgesic effect significantly, with a "U" shape curve. Interestingly, the hyperalgesic effect induced by EKA/B could be attenuated by SR140333B, SR142801 but not SR48968C. I.c.v. administration of EKC/D (1, 3, 12, 20nmol/mouse) also dose dependently induced analgesic effect, which could not be blocked by SR48968C or SR142801 or naloxone. But to our astonishment, it could be significantly enhanced by SR140333B. More interestingly, the hyperalgesic effect induced by EKA/B could be significantly attenuated by EKC/D. In addition, the analgesic effect induced by co-administration of EKA/B and EKC/D was much less stronger than the effect of either EKA/B or EKC/D.
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, China.
Yinliang
Y
Yang
Shouliang
S
Dong
D000700:Analgesics / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009270:Naloxone / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D010880:Piperidines / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015320:Tachykinins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D014326:Tropanes / Q000378:metabolism
D000700:Analgesics; D014150:Antipsychotic Agents; D001549:Benzamides; D009270:Naloxone; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018039:Receptors, Tachykinin; D015320:Tachykinins; D014326:Tropanes; C526005:SR140333B; C073839:SR 48968; C091554:SR 142801; C486037:TAC4 protein, human