Phospholipase A2 and 3H-hemicholinium-3 binding sites in rat brain: A potential second-messenger role for fatty acids in the regulation of high-affinity choline uptake

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Journal of Neuroscience; (USA)

OSTI ID:6994755

Saltarelli, M D; Yamada, K; Coyle, J T ^[1]

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1. Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)

The involvement of phospholipase A2 (PLA2) and fatty acid release in the regulation of sodium-dependent high-affinity choline uptake in rat brain was assessed in vitro through the use of the specific binding of 3H-hemicholinium-3 (3H-HCh-3). Addition of arachidonic acid and other unsaturated fatty acids to rat striatal membranes in vitro resulted in a dose-dependent, temperature-independent activation of 3H-HCh-3 binding. Scatchard analysis revealed that these changes in binding result from a 2-fold increase in the affinity and capacity of 3H-HCh-3 binding. Saturated fatty acids, lysophospholipids, and phospholipids did not affect specific 3H-HCh-3 binding. Addition of defatted BSA to membranes, which had been treated previously with arachidonic acid, completely reversed the increase in specific 3H-HCh-3 binding. However, several inhibitors of fatty acid metabolism, including nordihydroguaiaretic acid, indomethacin, catalase, and superoxide dismutase, did not alter arachidonic acid-induced changes in 3H-HCh-3 binding, suggesting that unsaturated fatty acids, and not their metabolites, are directly responsible for the observed activation of specific 3H-HCh-3 binding. Additionally, unsaturated fatty acids dose-dependently inhibited high-affinity 3H-choline uptake in rat striatal synaptosomes, apparently due to the disruption of synaptosomal integrity. The phospholipase A2 inhibitors quinacrine hydrochloride, trifluoperazine, and 4-bromophenacylbromide dose-dependently inhibited potassium depolarization-induced activation of specific 3H-HCh-3 binding in slices of rat brain in vitro. Similarly, both quinacrine and trifluoperazine inhibited the metabolism of phospholipids and the release of fatty acids evoked by either elevated KCl or calcium ionophore A23187.

• OSTI ID: 6994755
• Journal Information: Journal of Neuroscience; (USA), Journal Name: Journal of Neuroscience; (USA) Vol. 10:1; ISSN JNRSD; ISSN 0270-6474
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
BRAIN
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHOLINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
ESTERASES
ESTERS
FUNCTIONS
HYDROGEN COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
KINETICS
LIPASES
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PROTEINS
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES