Altered synaptosomal phospholipid metabolism after toluene: possible relationship with membrane fluidity, Na+,K(+)-adenosine triphosphatase and phospholipid methylation.
The mechanism by which toluene decreased synaptosomal phosphatidylethanolamine (PE) was investigated by studying degradative and synthetic phospholipid pathways. Toluene stimulated a PE-specific phospholipase (PLase) C both in vivo (44-75%) and in vitro (20-30%) whereas PLase A, PLase D and base exchange enzymes were unchanged. Toluene, in vivo, also increased the synthesis of PE (27%) when expressed as [3H]ethanolamine incorporation into [3H]PE, but had no effect on PE synthesis when administered in vitro. Perhaps this reflects a compensatory mechanism in synaptosomes to replace PE via increasing de novo synthesis. Phospholipid methylation, an event proposed to be related to the transduction of singals across membranes, as well as a measure of membrane function, was studied. Toluene was found to rapidly increase phospholipid methylation (43%, 15 min), followed by a significant decrease (35%, 1 hr). Another measure of membrane, as well as cell function used in these studies was ATPase activity. Toluene, both in vivo and in vitro, stimulated Na+, K(+)-adenosine triphosphatase (ATPase) activity (20-30%, 15-30 min), whereas Mg(++)-ATPase and Ca(++)-ATPase were unaffected, an indication that toluene alters neuronal cell function. Membrane fluidity studies using fluorescence polarization reported that toluene, both in vivo and in vitro, increased the outer synaptosomal membrane fluidity using the probe trimethylammonium-diphenylhexatriene, whereas no effect was observed on the central core fluidity using diphenylhexatriene. These are the first studies to demonstrate that an organic solvent effects only specific membrane region fluidities. One possibility is that early synaptic alterations resulting from toluene exposure may be preceded by increases in outer membrane fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)
Lebel
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Toxicology Program, Northeastern University, Boston, Massachusetts.
Schatz
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D000818:Animals; D007274:Injections, Intraperitoneal; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008745:Methylation; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology; D014050:Toluene / Q000494:pharmacology*
D010714:Phosphatidylethanolamines; D010743:Phospholipids; D014050:Toluene; D000254:Sodium-Potassium-Exchanging ATPase