Dipalmitoylphosphatidylcholine liposomes inhibit calcium-dependent [3H]acetylcholine release.

We examined the effects of small unilamellar vesicles composed of dipalmitoylphosphatidylcholine on rat cerebral cortical [3H]acetylcholine release. Synaptosomes from this region were loaded with the labeled transmitter, and then incubated with the lipid (0-6 mg/ml) for specified intervals before adding various secretagogues. Liposomes (0.4 mg/ml-6 mg/ml) inhibited the calcium-dependent release of [3H]acetylcholine induced by 50 mM K+, A23187 (1-5 micrograms/ml) or 500 microM ouabain; the calcium-independent release induced by ouabain was not affected by the highest liposome concentration studied (6 mg/ml). [3H]Acetylcholine levels were also reduced by the liposomes, but higher concentrations were necessary to do so than to reduce K+-induced release. These reductions occurred in the S3 (cytosol) but not P3 (microsomal) subcellular fraction of the nerve terminals. The 50 mM K+-induced induced release of [3H]norepinephrine and [3H]dopamine from cerebral cortical and striatal synaptosomes, respectively, were not affected by 6 mg/ml lipid. Together, these results suggest that the dipalmitoylphosphatidylcholine liposomes may modulate cholinergic transmission presynaptically at the level of the calcium-dependent transmitter-release process.