title: Reduction of Na+ enhances phosphoinositide hydrolysis and differentiates the stimulatory and inhibitory responses to quisqualate in rat brain slices.
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 (beta-N-oxalyl-L-alpha, beta-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.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
authors.forename: R S
authors.initials: RS
authors.lastname: Jope
authors.forename: X H
authors.initials: XH
authors.lastname: Li
authors.forename: G C
authors.initials: GC
authors.lastname: Ormandy
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.forename: M B
authors.initials: MB
authors.lastname: Williams
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium
chemical_list: D010716:Phosphatidylinositols; D014316:Tritium; D013779:Tetrodotoxin; D016318:Quisqualic Acid; D012964:Sodium