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Vol. 281, Issue 1, 448-453, 1997
Departments of
Medical Physiology (C.J.M., G.W.) and
Animal Science
(G.W.) Texas A&M University, College Station, Texas
This study was conducted to test the hypothesis that
L-glutamine has differential effects on nitric oxide (NO)
synthesis from L-arginine in bovine venular endothelial
cells (EC) stimulated by A23187 (a Ca++
ionophore) and receptor-mediated vasodilators (bradykinin and substance
P). EC were cultured at 37°C for 24 h in the presence of 0.4 mM
L-arginine and 0.0 to 2.0 mM L-glutamine with
or without 1 µM A23187, 1 µM bradykinin or 10 µM
substance P. The release of nitrite and nitrate by EC was used as an
indicator of NO synthesis. A23187, bradykinin or substance
P increased NO synthesis from L-arginine by EC in the
presence or absence of L-glutamine. The addition of
L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and
L-aspartate and decreased NO synthesis by EC in a
concentration-dependent manner in the presence or absence of
A23187, bradykinin or substance P. L-Glutamine
had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither
L-glutamine nor its glutaminase metabolites (ammonia,
L-glutamate and L-aspartate) had any effect on
endothelial NO synthase activity. Taken together, these results suggest
that the inhibition by L-glutamine of NO synthesis from
L-arginine is unlikely to result from an effect of
L-glutamine on L-arginine transport or NO
synthase activity. Although the mechanism involved remains unknown,
regulation of the arginine-NO pathway by L-glutamine may
have pharmacologic and therapeutic implications in such conditions as
inflammation and septic shock by inhibiting NO generation from
L-arginine in endothelial cells.
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