Fluoride-induced depletion of polyphosphoinositides in rat brain cortical slices: A rationale for the inhibitory effects on phospholipase C

Elisabet Sarri, Enrique Claro

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6 Citations (Scopus)

Abstract

Fluoride, which is used commonly as a pharmacological tool to activate phosphoinositide-phospholipase C coupled to the heterotrymeric G(q/11) proteins, inhibited the phosphorylation of phosphatidylinositol (PtdIns) to polyphosphoinositides (PtdIns4P and PtdIns4,5P2) in membranes from rat brain cortex. Fluoride enhanced basal production of 3H-inositol phosphates in membranes prepared from brain cortical slices that had been prelabeled with [3H]inositol, but inhibited the stimulation elicited by carbachol in the presence of GTPγS. However in both cases fluoride depleted [3H]PtdIns4P content by 95%. The inhibitory effects of fluoride on the release of 3H-inositol phosphates in slices were not apparent in a pulse [3H]inositol-labeling strategy, but became dramatic in a continuous labeling protocol, particularly at long incubation times. Prelabeling slices with [3H]inositol in the presence of fluoride precluded polyphosphoinositide labeling, and eliminated phospholipase C responsiveness to carbachol under normal or depolarizing conditions, and to the calcium ionophore ionomycin. The lack of response of 3H-polyphosphoinositide-depleted slices to phospholipase C stimuli was not due to fluoride poisoning, unaccesibility of the [3H]inositol label to phospholipase C or desensitization of G(q/11), as the effect of carbachol and GTPγS was restored, in the presence of ATP, in membranes prepared from slices that had been labeled in the presence of fluoride. In conclusion, our data show that fluoride, at a concentration similar to that used to stimulate directly G(q/11)-coupled phospholipase C, effectively blocks the synthesis of phospholipase C substrates from PtdIns. Copyright (C) 1999 ISDN.
Original languageEnglish
Pages (from-to)357-367
JournalInternational Journal of Developmental Neuroscience
Volume17
DOIs
Publication statusPublished - 9 Aug 1999

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