Dipalmitoylphosphatidylcholine liposomes reduce [3H]acetylcholine levels in an eserine-sensitive manner in rat cerebral cortical synaptosomes.
We investigated the effects of various phospholipids on the presynaptic levels of newly synthesized [3H]acetylcholine (ACh) in rat cerebral cortical synaptosomes. When administered as small unilamellar vesicles (200-500 A diameters) dipalmitoylphosphatidylcholine (DPPC) reduced [3H]ACh levels in concentration and time-related manners, while increasing the efflux of labelled choline to a similar extent. The reductions in synaptosomal [3H]-ACh levels induced by DPPC (3 mg/ml) were found in the cytosolic S3 but not microsomal P3 fraction, arguing for a cytoplasmic, non-vesicular site of action. DPPC-induced reductions in [3H]ACh levels were blocked by 100 microM eserine, a tertiary amine cholinesterase inhibitor, but not with 100 microM neostigmine, a quaternary ammonium inhibitor. Large unilamellar vesicles (2000-5000 A diameters) consisting of soybean-phosphatidylcholine reduced [3H]ACh levels to the same extent that small vesicles did at the same concentration (3 mg/ml). Taken together, these results suggest that DPPC can fuse with membranes to increase the hydrolysis of cytoplasmic ACh via a small intra-terminal subpopulation of cholinesterases.
Bottiglieri
D
D
Department of Pharmacology and Therapeutics, University of Florida School of Medicine, Gainesville 32610.
Meyer
E M
EM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D008081:Liposomes; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; D010830:Physostigmine; D002794:Choline; D000109:Acetylcholine