PMID- 27323834
OWN - NLM
STAT- MEDLINE
DCOM- 20180205
LR  - 20220408
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 34
DP  - 2016 Aug 23
TI  - Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential 
      and consequences of dysfunction.
PG  - 55840-55862
LID - 10.18632/oncotarget.10095 [doi]
AB  - Glutamate is probably the most important excitatory neurotransmitter in the 
      brain. The glutamate N-methyl-D-aspartate receptor (NMDAR) is a calcium-gated 
      channel that coordinates with G protein-coupled receptors (GPCRs) to establish 
      the efficiency of the synaptic transmission. Cross-regulation between these 
      receptors requires the concerted activity of the histidine triad 
      nucleotide-binding protein 1 (HINT1) and of the sigma receptor type 1 (sigma1R). 
      Essential brain functions like learning, memory formation and consolidation, mood 
      and behavioral responses to exogenous stimuli depend on the activity of NMDARs. 
      In this biological context, endocannabinoids are released to retain NMDAR 
      activity within physiological limits. The efficacy of such control depends on 
      HINT1/sigma1R assisting in the physical coupling between cannabinoid type 1 receptors 
      (CB1Rs) and NMDARs to dampen their activity. Subsequently, the calcium-regulated 
      HINT1/sigma1R protein tandem uncouples CB1Rs to prevent NMDAR hypofunction. Thus, 
      early recruitment or a disproportionate cannabinoid induced response can bring 
      about excess dampening of NMDAR activity, impeding its adequate integration with 
      GPCR signaling. Alternatively, this control circuit can apparently be overridden 
      in situations where bursts of NMDAR overactivity provoke convulsive syndromes. In 
      this review we will discuss the possible relevance of the HINT1/sigma1R tandem and 
      its use by endocannabinoids to diminish NMDAR activity and their implications in 
      psychosis/schizophrenia, as well as in NMDAR-mediated convulsive episodes.
FAU - Rodriguez-Munoz, Maria
AU  - Rodriguez-Munoz M
AD  - Department of Molecular, Cellular and Developmental Neurobiology, Laboratory of 
      Neuropharmacology, Instituto Cajal, Consejo Superior de Investigaciones 
      Cientificas (CSIC), Madrid, Spain.
FAU - Sanchez-Blazquez, Pilar
AU  - Sanchez-Blazquez P
AD  - Department of Molecular, Cellular and Developmental Neurobiology, Laboratory of 
      Neuropharmacology, Instituto Cajal, Consejo Superior de Investigaciones 
      Cientificas (CSIC), Madrid, Spain.
FAU - Merlos, Manuel
AU  - Merlos M
AD  - Drug Discovery & Preclinical Development, Esteve, Barcelona, Spain.
FAU - Garzon-Nino, Javier
AU  - Garzon-Nino J
AD  - Department of Molecular, Cellular and Developmental Neurobiology, Laboratory of 
      Neuropharmacology, Instituto Cajal, Consejo Superior de Investigaciones 
      Cientificas (CSIC), Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Cannabinoids)
RN  - 0 (Endocannabinoids)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Cannabinoids/therapeutic use
MH  - Endocannabinoids/*physiology
MH  - Epilepsy/drug therapy/physiopathology
MH  - Humans
MH  - Receptor Cross-Talk
MH  - Receptor, Cannabinoid, CB1/physiology
MH  - Receptors, G-Protein-Coupled/physiology
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Schizophrenia/drug therapy
PMC - PMC5342457
OTO - NOTNLM
OT  - GPCR-NMDAR coordination
OT  - HINT1 protein
OT  - convulsive disorders
OT  - mood disorders
OT  - sigma1R
COIS- CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
EDAT- 2016/06/22 06:00
MHDA- 2018/02/06 06:00
PMCR- 2016/08/23
CRDT- 2016/06/22 06:00
PHST- 2016/01/22 00:00 [received]
PHST- 2016/06/06 00:00 [accepted]
PHST- 2016/06/22 06:00 [pubmed]
PHST- 2018/02/06 06:00 [medline]
PHST- 2016/06/22 06:00 [entrez]
PHST- 2016/08/23 00:00 [pmc-release]
AID - 10095 [pii]
AID - 10.18632/oncotarget.10095 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Aug 23;7(34):55840-55862. doi: 10.18632/oncotarget.10095.