| Phospholipids are the major lipids in the plasma membrane, and it is now evident that the function of phospholipids exceeds that of the role of barrier between different aqueous compartments. Several lines of evidence suggest that a major plasma membrane lipid, phosphatidylcholine, may be a useful compound for modulating presynaptic cholinergic transmission. Phosphatidylcholine (PC) has been shown to activate membrane proteins such as acetylcholinesterase; provide more substrate, choline, for ACh synthesis; alter membrane fluidity; and affect receptor subunit interactions. In order to investigate the effects of PC on cholinergic terminals, rat cortical synaptosomes were preloaded with ('3)H -ACh and then treated with small unilamellar vesicles (SUV) composed of dipalmitoylphosphatidylcholine (DPPC) at concentrations (0.8-1.5 mg/ml) similar to those found circulating in plasma. The effects of DPPC on levels, hydrolysis, release, and synthesis of ('3)H -ACh were then examined. Dipalmitoylphosphatidylcholine decreased the levels of ('3)H -ACh. This decrease does not result from a dilution of the radioactive ('3)H -choline by nonradioactive choline derived from PC. Specifically, it is the S(,3) (cytoplasmic) level of ('3)H -ACh that is decreased by DPPC treatment. This decrease appears to be partially due to lipid activation of an intraterminal cholinesterase which results in hydrolysis of nonvesicular ('3)H -ACh. The lipid, DPPC, also blocks the K('+)-depolarization and A23187-induced release of ('3)H -ACh, perhaps by interfering with the Ca('2+)-induced exocytotic release process. The ability of the lipid to interfere with exocytosis may account for the blockade of the K('+) induced ('3)H -ACh release from the P(,3) (vesicular) fraction. The high affinity choline transporter was competitively inhibited by DPPC treatment when synaptosomes were treated with DPPC prior to ('3)H -choline loading; the ubiquitous low affinity transport was not affected. These effects were specific for cholinergic neurons since the uptake and release of dopamine and norepinephrine from the substantia nigra and the cortex, respectively, were not affected. |
