Anesthetic activity of monoketones in mice: relationship to hydrophobicity and in vivo effects on Na+/K+-ATPase activity and membrane fluidity

Anesthetic activity of monoketones in mice: relationship to hydrophobicity and in vivo effects on Na+/K+-ATPase activity and membrane fluidity

Tanii H

Toxicology Letters

1996

Anesthetics; Adenosinetriphosphatase; Hydrophobicity; Ketones; Membrane fluidity; Structure-Activity Relationship

The in vivo anesthetic activity of monoketones in mice was examined in relation to their hydrophobicity and to the in vivo effects on Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) activity and membrane fluidity. Anesthetic potency (AD50) of monoketones was determined; AD50 implys the dose required to anesthetize 50% of the animals from the treated group. The n-octanol/water partition coefficient (P) was used as an index of hydrophobicity. Membrane fluidity was determined by using 1,6-diphenyl-1,3,5-hexatriene (DPH) or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH as fluorescence probes. Log (1/AD50) was the parabolic function of log P log to be 2.09. Brain synaptosomes were prepared from mice that were considered anesthetized with each of the 4 monoketones (1.5 fold AD50), methyl n-propyl, mehtyl n-amyl, methyl 3-methylhexyl and methyl n-octyl ketone. The Na+/K+-ATPase activity was inhibited by methyl n-propyl ketone alone, membrane DPH fluidity was decreased by each of the 4 monoketones, and membrane TMA-DPH fluidity was decreased by methyl n-propylketone alone. These results suggest an involvement of the decreased DPH fluidity in monoketone-induced anesthesia.

1996

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