Effects of amiloride and dibucaine on a model phospholipid membrane— Structure-activity relationships

Abstract

The local anesthetic dibucaine, and the diuretic agent, amiloride, both decrease the negative surface charge of phospholipid membranes composed of phosphatidylcholine and dicetylphosphate. However, whereas dibucaine decreases the 22Na permeability of these structures, amiloride brings about an increase. The incorporation of cholesterol into such membranes normally reduces cation permeability, primarily through alterations in membrane viscosity. However, amiloride becomes even more effective in increasing 22Na movement in cholesterol-rich membranes; dibucaine, rather than reducing sodium permeability, actually causes an increase under these circumstances. It is proposed that dibucaine is buried in the membrane with its positively charged end anchored at the interface. The resultant alteration in surface charge reduces cation movement. On the other hand, amiloride is probably confined to the interfacial region, bound there by the electrostatic attraction between its positively charged amidino group and the phosphate ion of the phospholipid. The exact means by which this agent increases cation permeability is unclear, but probably involves changes localized to the interface.