Lipid modulation of neuronal cholinergic activity
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 lipids, phosphatidylcholine, may be a useful compound for modulating presynaptic cholinergic transmission. In order to investigate the effects of PC on cholinergic terminals, rat cortical synaptosomes were preloaded with (/sup 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 (/sup 3/H)-ACh were then examined. Dipalmitoylphosphatidylcholine decreased the levels of (/sup 3/H)-ACh. This decrease does not result from a dilution of the radioactive (/sup 3/H)-choline by nonradioactive choline derived from PC. Specifically, it is the S/sub 3/ (cytoplasmic) level of (/sup 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 (/sup 3/H)-ACh. The ability of the lipid to interfere with exocytosis may account for the blockade of the K/sup +/ induced (/sup 3/H)-ACh release from the P/sub 3/ (vesicular) fraction. The high affinity choline transporter was competitively inhibited by DPPC treatment when synaptosomes were treated with DPPC prior to (/sup 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.
- Research Organization:
- Florida Univ., Gainesville (USA)
- OSTI ID:
- 6717605
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
NERVE CELLS
PHYSIOLOGY
PHOSPHOLIPIDS
BIOSYNTHESIS
TRITIUM COMPOUNDS
CELL MEMBRANES
CHOLINE
CHOLINESTERASE
DOPAMINE
ENZYMATIC HYDROLYSIS
ENZYME ACTIVITY
MEMBRANE TRANSPORT
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLESTERASES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
HYDROLYSIS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
LYSIS
MEMBRANES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHENOLS
POLYPHENOLS
QUATERNARY COMPOUNDS
SOLVOLYSIS
SOMATIC CELLS
SYMPATHOMIMETICS
SYNTHESIS
551001* - Physiological Systems- Tracer Techniques