PMID- 33003406
OWN - NLM
STAT- MEDLINE
DCOM- 20210301
LR  - 20210301
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 19
DP  - 2020 Sep 29
TI  - Cross-Talk between P2X and NMDA Receptors.
LID - 10.3390/ijms21197187 [doi]
LID - 7187
AB  - Purinergic P2X receptors (P2X) are ATP-gated ion channels widely expressed in the 
      CNS. While the direct contribution of P2X to synaptic transmission is uncertain, 
      P2X reportedly affect N-methyl-D-aspartate receptor (NMDAR) activity, which has 
      given rise to competing theories on the role of P2X in the modulation of 
      synapses. However, P2X have also been shown to participate in receptor 
      cross-talk: an interaction where one receptor (e.g., P2X2) directly influences 
      the activity of another (e.g., nicotinic, 5-HT3 or GABA receptors). In this 
      study, we tested for interactions between P2X2 or P2X4 and NMDARs. Using 
      two-electrode voltage-clamp electrophysiology experiments in Xenopus laevis 
      oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an 
      inhibited manner. When investigating the molecular domains responsible for this 
      phenomenon, we found that the P2X2 c-terminus (CT) could interfere with both P2X2 
      and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on 
      the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of 
      these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 
      or P2X4. Collectively, these results provide new evidence for the modulatory 
      nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the 
      CNS.
FAU - Rodriguez, Larry
AU  - Rodriguez L
AUID- ORCID: 0000-0002-9591-5005
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Yi, Catherine
AU  - Yi C
AUID- ORCID: 0000-0002-5616-1239
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Chu, Cameron
AU  - Chu C
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Duriez, Quentin
AU  - Duriez Q
AD  - Univ. de Bordeaux, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000 
      Bordeaux, France.
AD  - CNRS, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000 Bordeaux, 
      France.
FAU - Watanabe, Sharyse
AU  - Watanabe S
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Ryu, Megan
AU  - Ryu M
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Reyes, Brandon
AU  - Reyes B
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, Los Angeles, CA 90033, USA.
FAU - Asatryan, Liana
AU  - Asatryan L
AD  - Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of 
      Southern California, Los Angeles, CA 90033, USA.
FAU - Boue-Grabot, Eric
AU  - Boue-Grabot E
AUID- ORCID: 0000-0003-2187-9037
AD  - Univ. de Bordeaux, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000 
      Bordeaux, France.
AD  - CNRS, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000 Bordeaux, 
      France.
FAU - Davies, Daryl
AU  - Davies D
AD  - Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of 
      Southern California, Los Angeles, CA 90033, USA.
LA  - eng
GR  - LR2017-2020/American Foundation for Pharmaceutical Education/
GR  - R01AA022448/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20200929
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (NMDA receptor A1)
RN  - 0 (Receptors, GABA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Purinergic P2X)
RN  - 0 (Receptors, Purinergic P2X4)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Neurons/metabolism
MH  - Oocytes/metabolism
MH  - Patch-Clamp Techniques
MH  - Receptor Cross-Talk/physiology
MH  - Receptors, GABA/genetics
MH  - Receptors, N-Methyl-D-Aspartate/*genetics
MH  - Receptors, Purinergic P2X/*genetics
MH  - Receptors, Purinergic P2X4/genetics
MH  - Synapses/*genetics
MH  - Synaptic Transmission/genetics
MH  - Xenopus laevis/genetics/physiology
PMC - PMC7582700
OTO - NOTNLM
OT  - NMDA receptors
OT  - P2X2 receptors
OT  - P2X4 receptors
OT  - cross-talk
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/10/03 06:00
MHDA- 2021/03/02 06:00
PMCR- 2020/10/01
CRDT- 2020/10/02 01:01
PHST- 2020/07/31 00:00 [received]
PHST- 2020/09/18 00:00 [revised]
PHST- 2020/09/25 00:00 [accepted]
PHST- 2020/10/02 01:01 [entrez]
PHST- 2020/10/03 06:00 [pubmed]
PHST- 2021/03/02 06:00 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - ijms21197187 [pii]
AID - ijms-21-07187 [pii]
AID - 10.3390/ijms21197187 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Sep 29;21(19):7187. doi: 10.3390/ijms21197187.