PMID- 7832303
OWN - NLM
STAT- MEDLINE
DCOM- 19950217
LR  - 20190628
IS  - 0003-3022 (Print)
IS  - 0003-3022 (Linking)
VI  - 82
IP  - 1
DP  - 1995 Jan
TI  - Ketamine inhibits glutamate-, N-methyl-D-aspartate-, and quisqualate-stimulated 
      cGMP production in cultured cerebral neurons.
PG  - 205-13
AB  - BACKGROUND: Glutamatergic signaling has been linked to the recently discovered 
      neurotransmitter/neuromodulator nitric oxide (NO), and several classes of 
      anesthetics block some step in glutamatergic signaling. This study was designed 
      to determine whether or not ketamine would prevent NO-dependent cGMP production 
      stimulated by glutamate (GLU) and the GLU analogs NMDA, quisqualate (QUIS), and 
      kainate (KAIN). METHODS: Primary cultures of cortical neurons and glia (prepared 
      from 16-day gestational rat fetuses) were used after 12-16 days in culture. 
      Reactions were carried out in magnesium-free buffer containing 100 microM 
      3-isobutyl-1-methylxanthine, and cGMP content of cultures was used as a bioassay 
      of NO production. RESULTS: Cyclic GMP production stimulated by sodium 
      nitroprusside (100 microM) occurred predominately in neurons and not in glia. 
      Neurons were spontaneously active in these cultures; basal cGMP production was 
      decreased by 50% in the presence of 1 microM tetrodotoxin (TTX). Glutamate (100 
      microM), NMDA (100 microM), QUIS (300 microM), and KAIN (100 microM) each 
      increased cGMP content of neuronal cultures. L-NMMA (100 microM), a NO synthase 
      inhibitor, prevented the stimulation of cGMP production by GLU or its analogs. 
      Pretreatment with MK-801 (1 microM) or ketamine (10-100 microM) inhibited GLU-, 
      NMDA-, and QUIS-stimulated cGMP production. Quisqualate-stimulated responses were 
      the most sensitive to inhibition by ketamine and NMDA-stimulated responses were 
      the least sensitive to inhibition. MK-801 and ketamine did not significantly 
      inhibit KAIN-stimulated cGMP production. CNQX (10 microns) blocked 
      KAIN-stimulated cGMP production only. CONCLUSIONS: The authors' data demonstrate 
      that ketamine inhibited NO synthesis stimulated by NMDA- and non-NMDA-receptor 
      specific analogs. Our findings indicate that blockade of QUIS- as well as 
      NMDA-subtypes of GLU- receptor may be important in the development of 
      ketamine-induced anesthesia.
FAU - Gonzales, J M
AU  - Gonzales JM
AD  - Department of Anesthesia, University of Pennsylvania, Philadelphia.
FAU - Loeb, A L
AU  - Loeb AL
FAU - Reichard, P S
AU  - Reichard PS
FAU - Irvine, S
AU  - Irvine S
LA  - eng
GR  - R01-GM43969/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 690G0D6V8H (Ketamine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 8OC22C1B99 (Quisqualic Acid)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Brain/cytology/drug effects
MH  - Cells, Cultured
MH  - Cyclic GMP/*biosynthesis
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glutamic Acid/*pharmacology
MH  - Ketamine/*pharmacology
MH  - N-Methylaspartate/*antagonists & inhibitors
MH  - Neurons/*drug effects/metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Nitroprusside/pharmacology
MH  - Quisqualic Acid/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1097/00000542-199501000-00025 [doi]
PST - ppublish
SO  - Anesthesiology. 1995 Jan;82(1):205-13. doi: 10.1097/00000542-199501000-00025.