Mechanism of modification of rat brain lysophospholipase A activity by cationic amphiphilic drugs

Abstract

The three psychotropic cationic amphiphilic drugs, chlorpromazine, desmethylimipramine and propranolol were found to have biphasic effects on rat brain lysophospholipase A, stimulating the enzyme at low, and inhibiting it non-competitively at higher concentrations. Low concentrations (less than or equal to 50 microM) of the drugs prevented the formation of micelles of lysophosphatidylcholine, whereas high concentrations caused a phase transition of the substrate with formation of a highly ordered membranous lattice. A possible mechanism of stimulation and inhibition of the enzyme activity by cationic amphiphilic drugs is proposed. Stimulation is explained by a decrease in the concentration of substrate micelles, which are inhibitory for the activity, whereas inhibition may be caused by adsorption of the enzyme onto the membranous lattice formed by the substrate in the presence of high cationic amphiphilic drug concentrations.