Reduction of Na+ enhances phosphoinositide hydrolysis and differentiates the stimulatory and inhibitory responses to quisqualate in rat brain slices

Richard S Jope, Xiaohua Li, George C. Ormandy, Ling Song, Mary B. Williams

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalBrain Research
Volume536
Issue number1-2
DOIs
StatePublished - Dec 17 1990
Externally publishedYes

Fingerprint

Quisqualic Acid
Phosphatidylinositols
Hydrolysis
Brain
Norepinephrine
Inositol
Carbachol
Acids

Keywords

  • Excitatory amino acid
  • Inositol phosphate
  • Norepinephrine
  • Quisqualate
  • Sodium-dependent

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Reduction of Na+ enhances phosphoinositide hydrolysis and differentiates the stimulatory and inhibitory responses to quisqualate in rat brain slices. / Jope, Richard S; Li, Xiaohua; Ormandy, George C.; Song, Ling; Williams, Mary B.

In: Brain Research, Vol. 536, No. 1-2, 17.12.1990, p. 251-256.

Research output: Contribution to journalArticle

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abstract = "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.",
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