Physical-chemical-activity relationship of organic solvents: effects on Na(+)-K(+)-ATPase activity and membrane fluidity in mouse synaptosomes.
Physical-chemical-activity relationship of aromatic hydrocarbons (n = 10) and alkyl acetates (n = 16) with respect to their in vitro effects on synaptosomal membranes was studied. Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity and membrane fluidity, which was determined using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene, were used as potential indicators of neuronal cell toxicity. The potency of inhibition for the enzyme (IC50), the potency of increasing membrane fluidity (IC12.5), and n-octanol/water partition coefficient (P) were all determined experimentally for 26 solvents. Correlation analyses were made on aromatic hydrocarbons and on alkyl acetates. There were linear relationships between log P and pIC50 (log1/IC50) values, and between log P and pIC12.5 (log1/IC12.5) values, indicating that the hydrophobicity of the solvents determines their toxic ability to affect membrane environment; the more hydrophobic the solvents are, the more toxic they are. A direct linear relationship between Na(+)-K(+)-ATPase activity pIC50 and membrane fluidity pIC12.5 values was also shown. This predictive correlation suggests a similar mechanism of membrane surface interaction govering both processes that are common to the test solvents. The present results confirm the importance of the lipid environment of neuronal membranes in maintaining the normal function of membrane-bound protein.
Tanii
H
H
Department of Hygiene, School of Medicine, Kanazawa University, Japan.
Huang
J
J
Ohyashiki
T
T
Hashimoto
K
K
D000085:Acetates / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004161:Diphenylhexatriene; D006838:Hydrocarbons / Q000737:chemistry / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D012997:Solvents / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000085:Acetates; D006838:Hydrocarbons; D012997:Solvents; D004161:Diphenylhexatriene; D000254:Sodium-Potassium-Exchanging ATPase