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Nitrous oxide (N 2 O) increases brain L‐arginine in production of its antinociceptive effect in mice
Author(s) -
Zhang Yao,
Sayre Casey L.,
Chung Eunhee,
Ohgami Yusuke,
Davies Neal M.,
Quock Raymond M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.662.8
Subject(s) - nociception , nitric oxide , arginine , chemistry , nitric oxide synthase , endocrinology , pharmacology , medicine , biochemistry , receptor , amino acid
C57BL/6 (C57) inbred mice respond to N 2 O with an increase in brain nitric oxide synthase (NOS) activity and a robust antinociceptive effect; DBA/2 (DBA) fail to exhibit these responses (Ishikawa and Quock, Brain Res. 976:262–263, 2003a). This study was conducted to determine whether increasing the availability of nitric oxide (NO) by administration of L‐arginine might increase responsiveness of DBA mice to N 2 O and ascertain the effect of N 2 O on brain levels of L‐arginine. Sensitivity to N 2 O was assessed using the acetic acid‐induced abdominal constriction test. Whole brain levels of L‐arginine were quantified by HPLC. Intracerebroventricular preloading of L‐arginine in subthreshold doses enhanced the N 2 O‐induced antinociceptive effects in both C57 and DBA mice. A 60‐min exposure to 70% N 2 O produced a 12‐fold increase in brain L‐arginine levels of C57 mice, compared to room air exposure. Similar treatment of DBA mice resulted in a 5‐fold increase in brain L‐arginine levels. While the cause of the differential responsiveness of inbred mice to N 2 O remains to be determined, it is apparent that N 2 O increases brain L‐arginine levels to produce its antinociceptive effect. (Supported in part by NIH Grant GM‐77153 and the Allen I. White Distinguished Professorship.)