PMID- 25445489
OWN - NLM
STAT- MEDLINE
DCOM- 20150715
LR  - 20150112
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 89
DP  - 2015 Feb
TI  - HINT1 protein: a new therapeutic target to enhance opioid antinociception and 
      block mechanical allodynia.
PG  - 412-23
AB  - In the nervous system, the glutamate N-methyl-D-aspartate receptor (NMDAR) 
      restricts the activity of the mu-opioid receptor (MOR). Both receptors are 
      present in midbrain periaqueductal grey (PAG) neurons, an area that plays a 
      central role in the supraspinal antinociceptive effects of opioids. The 
      cross-talk that occurs between these receptors is sustained by the MOR-associated 
      histidine triad nucleotide binding protein 1 (HINT1), which displays nucleoside 
      phosphoramidase and acyl-AMP hydrolase activity. Here we report that the 
      inhibitor of HINT1 enzymatic activity guanosine-5'-tryptamine carbamate (TpGc) 
      significantly enhanced morphine antinociception while preventing the development 
      of tolerance. At the molecular level, TpGc reduced the capacity of MORs to 
      recruit NMDAR activity to negatively regulate opioid signaling. In mice suffering 
      from chronic constriction injury concurrent with increased NMDAR activity, a 
      single intracerebroventricular administration of TpGc attenuated NMDAR function 
      and alleviated mechanical allodynia for several days. These data suggest a 
      potential therapeutic role for HINT1 inhibitors in the clinical management of 
      acute and neuropathic pain.
FAU - Garzon, Javier
AU  - Garzon J
AD  - Neuropharmacology, Instituto Cajal, Consejo Superior de Investigaciones 
      Cientificas (CSIC), Avda Dr. Arce 37, 28002 Madrid, Spain.
FAU - Herrero-Labrador, Raquel
AU  - Herrero-Labrador R
FAU - Rodriguez-Munoz, Maria
AU  - Rodriguez-Munoz M
FAU - Shah, Rachit
AU  - Shah R
FAU - Vicente-Sanchez, Ana
AU  - Vicente-Sanchez A
FAU - Wagner, Carston R
AU  - Wagner CR
FAU - Sanchez-Blazquez, Pilar
AU  - Sanchez-Blazquez P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Hint1 protein, mouse)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/*therapeutic use
MH  - Animals
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Drug Tolerance
MH  - Exploratory Behavior/drug effects
MH  - Hyperalgesia/*drug therapy/etiology
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Morphine/*therapeutic use
MH  - Motor Activity/drug effects
MH  - Nerve Tissue Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Neurons/drug effects
MH  - Peripheral Nerve Injuries/complications
MH  - Receptors, N-Methyl-D-Aspartate/genetics
MH  - Swimming/psychology
EDAT- 2014/12/03 06:00
MHDA- 2015/07/16 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/06/16 00:00 [received]
PHST- 2014/10/21 00:00 [revised]
PHST- 2014/10/27 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/07/16 06:00 [medline]
AID - S0028-3908(14)00397-9 [pii]
AID - 10.1016/j.neuropharm.2014.10.022 [doi]
PST - ppublish
SO  - Neuropharmacology. 2015 Feb;89:412-23. doi: 10.1016/j.neuropharm.2014.10.022.