Local Anesthetics and Antipsychotic XXXX Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in @entity375 .

@entity20491 @entity72733 @entity11922 @entity12015 @entity6513 @entity375 @entity413
UNASSIGNED: Action mechanisms of anesthetics remain unclear because of difficulty in explaining how structurally different anesthetics cause similar effects. In @entity375 , local anesthetics and antipsychotic @entity11922 induced responses similar to those caused by @entity413 starvation, and they eventually inhibited cell growth. These drugs inhibited @entity413 uptake but additional @entity413 conferred resistance to their effects; hence, the primary action of the drugs is to cause @entity413 starvation. In hxt(0) strains with all @entity12015 transporter (HXT) genes deleted, a strain harboring a single copy of @entity20491 ( @entity20491 ) was more sensitive to @entity6513 than a strain harboring multiple copies (HXT1m), which indicates that quantitative reduction of @entity20491 increases @entity6513 sensitivity. However, additional @entity413 rather than the overexpression of @entity72733 conferred @entity6513 resistance to wild-type @entity375 ; therefore, Hxts that actively transport hexoses apparently confer @entity6513 resistance. Additional @entity413 alleviated sensitivity to local anesthetics and @entity11922 in the HXT1m strain but not @entity20491 s strain; thus, the @entity413 -induced effects required a certain amount of @entity20491 . At low concentrations, fluorescent @entity11922 were distributed in various membranes. At higher concentrations, they destroyed the membranes and thereby delocalized @entity20491 -GFP from the plasma membrane, similar to local anesthetics. These results suggest that the aforementioned drugs affect various membrane targets via nonspecific interactions with membranes. However, the drugs preferentially inhibit the function of abundant Hxts, resulting in @entity413 starvation. When Hxts are scarce, this preference is lost, thereby losing the alleviation by additional @entity413 . These results provide a mechanism that explains how different compounds induce similar effects according to lipid theory.
