PMID- 17693030
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20181201
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 148
IP  - 4
DP  - 2007 Sep 21
TI  - Sex-dependent differences in the activity and modulation of N-methyl-d-aspartic 
      acid receptors in rat dorsal root ganglia neurons.
PG  - 1015-20
AB  - Women have greater temporal summation of experimental pain stimuli and also have 
      a higher propensity for developing chronic visceral pain conditions. Sex 
      hormone-mediated regulation of N-methyl-d-aspartic acid receptors (NMDARs) in 
      nociceptive pathways is a plausible mechanism that may underlie these phenomena. 
      The aim of this study was to compare the effect of 17-beta-estradiol (E2) in 
      modulation of NMDAR activity in adult male and female rat dorsal root ganglia 
      (DRG) neurons. DRG neurons were collected from adult male or female rats and 
      grown in short-term culture in steroid-free media. NMDAR currents were recorded 
      on small to medium size neurons by whole cell patch clamp using rapid perfusion 
      with saturating concentrations of N-methyl-d-aspartic acid and glycine in the 
      absence of extracellular Mg(2+). We found that the average density of NMDAR 
      currents was 2.8-fold larger in DRG neurons from female rats compared with male 
      rats (P<0.0001). Addition of 100 nM E2 increased NMDAR currents 55+/-15% in 
      female neurons, but only 19+/-7% in male neurons. Potentiation was maximal after 
      20-40 min and dose dependent with an apparent 50% excitatory concentration of 
      17-23 nM. This effect was mimicked by E2 conjugated to BSA and attenuated by 
      pretreatment with the protein tyrosine kinase inhibitor lavendustin A (1 microM) 
      or the estrogen receptor (ER) antagonist, ICI 182,780 (1 microM), strongly 
      suggesting activation of a cell surface ER acting through a non-genomic mechanism 
      involving protein tyrosine kinases to increase NMDAR currents. These results 
      identify sex-based differences in both the basal expression and the regulation of 
      the NMDARs in DRG neurons.
FAU - McRoberts, J A
AU  - McRoberts JA
AD  - Center for Neurovisceral Sciences and Women's Health, David Geffen School of 
      Medicine at UCLA, Warren Hall, Room 14-103, 900 Veteran Avenue, Los Angeles, CA 
      90095, USA. mcrobert@ucla.edu
FAU - Li, J
AU  - Li J
FAU - Ennes, H S
AU  - Ennes HS
FAU - Mayer, E A
AU  - Mayer EA
LA  - eng
GR  - R24 AT002681-04/AT/NCCIH NIH HHS/United States
GR  - R01 DK058173/DK/NIDDK NIH HHS/United States
GR  - 1 P50 DK64539/DK/NIDDK NIH HHS/United States
GR  - R24 AT002681/AT/NCCIH NIH HHS/United States
GR  - R01 DK058173-07/DK/NIDDK NIH HHS/United States
GR  - P50 DK064539/DK/NIDDK NIH HHS/United States
GR  - DK58173/DK/NIDDK NIH HHS/United States
GR  - P50 DK064539-06/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070712
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogens)
RN  - 0 (Excitatory Amino Acid Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Action Potentials/drug effects/*physiology/radiation effects
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Dose-Response Relationship, Radiation
MH  - Electric Stimulation/methods
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogens/pharmacology
MH  - Excitatory Amino Acid Agents/pharmacology
MH  - Female
MH  - Fulvestrant
MH  - Ganglia, Spinal/*cytology
MH  - Glycine/pharmacology
MH  - Male
MH  - N-Methylaspartate/pharmacology
MH  - Neurons/drug effects/*physiology/radiation effects
MH  - Patch-Clamp Techniques/methods
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - *Sex Characteristics
PMC - PMC2350242
MID - NIHMS31789
EDAT- 2007/08/19 09:00
MHDA- 2008/02/15 09:00
PMCR- 2008/04/28
CRDT- 2007/08/19 09:00
PHST- 2007/01/31 00:00 [received]
PHST- 2007/06/28 00:00 [revised]
PHST- 2007/07/11 00:00 [accepted]
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
PHST- 2008/04/28 00:00 [pmc-release]
AID - S0306-4522(07)00875-5 [pii]
AID - 10.1016/j.neuroscience.2007.07.006 [doi]
PST - ppublish
SO  - Neuroscience. 2007 Sep 21;148(4):1015-20. doi: 
      10.1016/j.neuroscience.2007.07.006. Epub 2007 Jul 12.