PMID- 18262387
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20161124
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 22
IP  - 6
DP  - 2008 Aug
TI  - In vivo characterization of the effects of human hemokinin-1 and human 
      hemokinin-1(4-11), mammalian tachykinin peptides, on the modulation of pain in 
      mice.
PG  - 850-60
LID - 10.1016/j.bbi.2007.12.010 [doi]
AB  - Human hemokinin-1 (h HK-1) and its truncated form h HK-1(4-11) are mammalian 
      tachykinin peptides encoded by the recently identified TAC4 gene in human, and 
      the biological functions of these peptides have not been well investigated. In 
      the present study, an attempt has been made to investigate the effects and 
      mechanisms of action of h HK-1 and h HK-1(4-11) in pain modulation at the 
      supraspinal level in mice using the tail immersion test. Intracerebroventricular 
      (i.c.v.) administration of h HK-1 (0.3, 1, 3 and 6 nmol/mouse) produced a dose- 
      and time-related antinociceptive effect. This effect was significantly 
      antagonized by the NK(1) receptor antagonist SR140333, but not by the NK(2) 
      receptor antagonist SR48968, indicating that the analgesic effect induced by 
      i.c.v. h HK-1 is mediated through the activation of NK(1) receptors. 
      Interestingly, naloxone, beta-funaltrexamine and naloxonazine, but not 
      naltrindole and nor-binaltorphimine, could also block the analgesic effect 
      markedly, suggesting that this effect is related to descending mu opioidergic 
      neurons (primary mu(1) subtype). Human HK-1(4-11) could also induce a dose- and 
      time-dependent analgesic effect after i.c.v. administration, however, the potency 
      of analgesia was less than h HK-1. Surprisingly, SR140333 could not modify this 
      analgesic effect, suggesting that this effect is not mediated through the NK(1) 
      receptors like h HK-1. SR48968 could modestly enhance the analgesic effect 
      induced by h HK-1(4-11), indicating that a small amount of h HK-1(4-11) may bind 
      to NK(2) receptors. Furthermore, none of the opioid receptor (OR) antagonists 
      could markedly block the analgesia of h HK-1(4-11), suggesting that the analgesic 
      effect is not mediated through the descending opioidergic neurons. Blocking of 
      delta ORs significantly enhanced the analgesia, indicating that delta OR is a 
      negatively modulatory factor in the analgesic effect of h HK-1(4-11). It is 
      striking that bicuculline (a competitive antagonist at GABA(A) receptors) 
      effectively blocked the analgesia induced by h HK-1(4-11), suggesting that this 
      analgesic effect is mediated through the descending inhibitory GABAergic neurons. 
      The novel mechanism involved in the analgesic effect of h HK-1(4-11), which is 
      different from that of h HK-1, may pave the way for a new strategy for the 
      investigation and control of pain.
FAU - Fu, Cai Y
AU  - Fu CY
AD  - State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department 
      of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 
      Kowloon, Hong Kong.
FAU - Zhao, You L
AU  - Zhao YL
FAU - Dong, Li
AU  - Dong L
FAU - Chen, Qiang
AU  - Chen Q
FAU - Ni, Jing M
AU  - Ni JM
FAU - Wang, Rui
AU  - Wang R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080208
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Analgesics)
RN  - 0 (Benzamides)
RN  - 0 (GABA Antagonists)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Neurokinin-1 Receptor Antagonists)
RN  - 0 (Peptide Fragments)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Neurokinin-2)
RN  - 0 (SR140333B)
RN  - 0 (TAC4 protein, human)
RN  - 0 (Tachykinins)
RN  - 0 (Tropanes)
RN  - 0 (hemokinin-1)
RN  - 36B82AMQ7N (Naloxone)
RN  - 5S6W795CQM (Naltrexone)
RN  - 720U2QK8I5 (SR 48968)
RN  - 72782-05-9 (beta-funaltrexamine)
RN  - 82824-01-9 (naloxonazine)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Analgesics/administration & dosage/pharmacology
MH  - Animals
MH  - Benzamides/pharmacology
MH  - Bicuculline/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - GABA Antagonists/pharmacology
MH  - Humans
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Naloxone/analogs & derivatives/pharmacology
MH  - Naltrexone/analogs & derivatives/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Neurokinin-1 Receptor Antagonists
MH  - Pain/physiopathology/*prevention & control
MH  - Pain Measurement/methods
MH  - Peptide Fragments/administration & dosage/*pharmacology
MH  - Piperidines/pharmacology
MH  - Receptors, Neurokinin-2/antagonists & inhibitors
MH  - Tachykinins/administration & dosage/chemistry/*pharmacology
MH  - Tropanes/pharmacology
EDAT- 2008/02/12 09:00
MHDA- 2008/08/13 09:00
CRDT- 2008/02/12 09:00
PHST- 2007/10/23 00:00 [received]
PHST- 2007/12/09 00:00 [revised]
PHST- 2007/12/22 00:00 [accepted]
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - S0889-1591(07)00343-1 [pii]
AID - 10.1016/j.bbi.2007.12.010 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2008 Aug;22(6):850-60. doi: 10.1016/j.bbi.2007.12.010. Epub 
      2008 Feb 8.