Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity.
This study investigated the effects of toluene (1 g/kg, 1 hr, i.p.) on rat synaptosomal phospholipid methylation (PLM), phospholipid composition, and membrane fluidity. Toluene significantly decreased basal PLM (35%) in studies using [3H]methionine [( 3H]Met) as the methyl donor; this was reflected by similar decreases in phosphatidylmonomethylethanolamine (PME) (30%). No effects were observed in either PLM reactions that used [3H]adenosylmethionine [( 3H]AdoMet) as methyl donor, or AdoMet synthetase, suggesting that toluene preferentially affects PLM reactions that derive methyl groups from [3H]Met. Also, toluene decreased synaptosomal phosphatidylethanolamine (PE) (24%), the initial substrate for PLM, and the addition of PE back to PE-depleted synaptosomes restored methyltransferase activity. Agonist-stimulated PLM using norepinephrine (NE) demonstrated that agonist-receptor coupling returned PLM to control values in synaptosomes from toluene-treated rats. NE-stimulated PLM was also blocked by propranolol (PRO), suggesting a role for toluene in receptor-mediated events. Membrane fluidity studies demonstrated that in vivo administration of toluene increased the outer synaptosomal membrane fluidity, whereas in vitro administration of toluene had no effect. Our observations support a positive relationship between increased PLM activity and increased outer, not core, membrane fluidity. These data demonstrate that specific toluene-phospholipid interactions occur in synaptosomes, resulting in altered membrane composition, function and fluidity.
LeBel
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CP
Toxicology Program, Northeastern University, Boston, MA 02115.
Schatz
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RA
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008715:Methionine / Q000378:metabolism; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008745:Methylation; D009638:Norepinephrine / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014050:Toluene / Q000494:pharmacology*
D010714:Phosphatidylethanolamines; D010743:Phospholipids; C032000:phosphatidyl-N-monomethylaminoethanol; D014050:Toluene; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D011433:Propranolol; D008715:Methionine; D008716:Methionine Adenosyltransferase; D009638:Norepinephrine