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Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein.

Abstract：

:The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prostacyclin (PGI2) by cultured human umbilical vein endothelial cells without evidence of cellular toxicity detected by 51Cr or lactate dehydrogenase release. PGI2 synthesis by NaF-stimulated endothelial cells was associated with increases in arachidonate release, phosphoinositide hydrolysis, generation of inositol phosphates, and accumulation of diacylglycerol. These responses to NaF, as well as alpha-thrombin-mediated responses, were not dependent upon the availability of extracellular free Ca2+ but were associated with the mobilization of stored intracellular Ca2+ detected by the luminescence of the photoprotein aequorin. Neither PGI2 synthesis nor Ca2+ responses following alpha-thrombin or NaF stimulation were inhibited by pretreatment of cells with the islet activating protein from Bordetella pertussis but were significantly attenuated by the G protein inhibitor GDP beta S in permeabilized cells. Our results are compatible with a model wherein NaF directly activates a phosphoinositidase-linked guanine nucleotide regulatory protein, Gp, in human umbilical vein endothelial cell monolayers. This activation results in phosphoinositide hydrolysis, Ca2+ mobilization, arachidonate release, and subsequent functional activation, assessed by PGI2 release. Biologically relevant agonists such as alpha-thrombin may exert their influence on arachidonate metabolism, in part, by promoting receptor-dependent activation of this G protein.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Garcia JG,Dominguez J,English D

doi

10.1165/ajrcmb/5.2.113

keywords:

subject

Has Abstract

pub_date

1991-08-01 00:00:00

pages

113-24

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

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Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein.