TY - JOUR
T1 - Reduction of Na+ enhances phosphoinositide hydrolysis and differentiates the stimulatory and inhibitory responses to quisqualate in rat brain slices
AU - Jope, Richard S.
AU - Li, Xiaohua
AU - Ormandy, George C.
AU - Song, Ling
AU - Williams, Mary B.
N1 - Funding Information:
Acknowledgements. The authors thank Dot McAdory for preparing the manuscript. This study was supported by USPHS grant NS-26165 and by the U.S. Army Medical Research and Development Command under contract No. DAMD-17-89-C-9037. Opinions, interpretations and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army.
PY - 1990/12/17
Y1 - 1990/12/17
N2 - The concentration of Na+ in the incubation medium significantly influenced phosphoinositide hydrolysis induced by some, but not all, agonists in rat cerebral cortical slices. Reductions of the Na+ concentration below 120 mM resulted in incremental increases in basal and norepinephrine-stimulated accumulation of [3H]inositol monophosphate in cortical slices that had been prelabelled with [3H]inositol, and maximal responses were obtained with 0 and 5 mM Na+. In contrast, the responses to carbachol and ibotenate were similar in medium containing 120 or 5 mM Na+. In medium with 120 mM Na+, quisqualate has two effects on phosphoinositide hydrolysis in cortical slices, including a relatively weak stimulatory effect and an inhibitory modulation of the stimulation induced by norepinephrine. These two responses to quisqualate were differentially modulated by Na+; in 5 mM compared with 120 mM Na+ the stimulatory response was greatly increased and the inhibitory effect was mostly eliminated. That these were two separate events was confirmed by the use of l-BOAA (β-N-oxalyl-l-α,β-diaminopropionic acid), which reproduces the inhibitory, but not the stimulatory effect of quisqualate on phosphoinositide hydrolysis. In 5 mM Na+, inhibition by l-BOAA of norepinephrine-stimulated phosphoinositide hydrolysis was completely eliminated. These results demonstrate that a physiological concentration of Na+ maintains phosphoinositide hydrolysis at a submaximal level of sensitivity to some, but not all, agonists. The differential effects of Na+ on the stimulatory and inhibitory effects of quisqualate further substantiate the suggestion that these are two separate processes and indicate that alterations of the Na+ concentration may influence the effects of quisqualate, and other agonists, on phosphoinositide hydrolysis.
AB - The concentration of Na+ in the incubation medium significantly influenced phosphoinositide hydrolysis induced by some, but not all, agonists in rat cerebral cortical slices. Reductions of the Na+ concentration below 120 mM resulted in incremental increases in basal and norepinephrine-stimulated accumulation of [3H]inositol monophosphate in cortical slices that had been prelabelled with [3H]inositol, and maximal responses were obtained with 0 and 5 mM Na+. In contrast, the responses to carbachol and ibotenate were similar in medium containing 120 or 5 mM Na+. In medium with 120 mM Na+, quisqualate has two effects on phosphoinositide hydrolysis in cortical slices, including a relatively weak stimulatory effect and an inhibitory modulation of the stimulation induced by norepinephrine. These two responses to quisqualate were differentially modulated by Na+; in 5 mM compared with 120 mM Na+ the stimulatory response was greatly increased and the inhibitory effect was mostly eliminated. That these were two separate events was confirmed by the use of l-BOAA (β-N-oxalyl-l-α,β-diaminopropionic acid), which reproduces the inhibitory, but not the stimulatory effect of quisqualate on phosphoinositide hydrolysis. In 5 mM Na+, inhibition by l-BOAA of norepinephrine-stimulated phosphoinositide hydrolysis was completely eliminated. These results demonstrate that a physiological concentration of Na+ maintains phosphoinositide hydrolysis at a submaximal level of sensitivity to some, but not all, agonists. The differential effects of Na+ on the stimulatory and inhibitory effects of quisqualate further substantiate the suggestion that these are two separate processes and indicate that alterations of the Na+ concentration may influence the effects of quisqualate, and other agonists, on phosphoinositide hydrolysis.
KW - Excitatory amino acid
KW - Inositol phosphate
KW - Norepinephrine
KW - Quisqualate
KW - Sodium-dependent
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U2 - 10.1016/0006-8993(90)90032-7
DO - 10.1016/0006-8993(90)90032-7
M3 - Article
C2 - 1964831
AN - SCOPUS:0025609404
VL - 536
SP - 251
EP - 256
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -