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

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.