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Toxicol Appl Pharmacol. 1994 Jun;126(2):352-60.

Phospholipid metabolism in neural microvascular endothelial cells after exposure to lead in vitro.

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1
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.

Abstract

Lead (Pb2+) is known to alter the permeability of brain capillaries. A possible mechanism for this alteration may be related to the ability of Pb2+ to substitute for Ca2+. Products derived from phospholipid metabolism, namely eicosanoids and diacylglycerol, control endothelial permeability, are partly regulated by intracellular Ca2+, and thus may be sensitive to Pb2+. We asked in this study whether Pb2+ increased arachidonic acid release or stimulated phosphatidylcholine breakdown in an in vitro model of brain capillaries, namely cultured bovine retinal endothelial (BRE) cells. Pb2+ stimulated arachidonic acid release and phosphatidylcholine and phosphatidylinositol metabolism in the presence of ionomycin, but not by itself. More arachidonic acid was released than phosphorylcholine in BRE cells stimulated with ionomycin and Pb2+, but the magnitudes of these responses were similar in cells exposed to ionomycin plus Ca2+. Ionomycin plus Pb2+ or plus Ca2+ resulted in the activation of phospholipase A2, since an increase in lysophosphatidylcholine and arachidonic acid was observed. Protein kinase C was not required for arachidonic acid release because release was observed in cells with a down-regulated enzyme. Ionomycin plus other metals (La3+, Cd2+, or Mg2+) did not result in arachidonic acid release, but Cd2+ or Co2+ inhibited arachidonic acid release by more than 80% when cells were exposed to ionomycin with either Pb2+ or Ca2+. Thapsigargin or maitotoxin plus Ca2+ increased arachidonic acid release that was inhibited by the receptor-dependent calcium channel antagonist SK&F 96365 but not by the voltage-dependent calcium channel antagonist nifedipine. However, thapsigargin or maitotoxin plus Pb2+ failed to stimulate arachidonic release. Since in this in vitro model Pb2+ stimulated phospholipid metabolism solely in the presence of an ionophore, the increase in permeability observed in Pb(2+)-exposed animals is probably not due to a release of metabolites of arachidonic acid.

PMID:
8209388
DOI:
10.1006/taap.1994.1126
[Indexed for MEDLINE]

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