Specificity of the activation of ( sup 3 H)hemicholinium-3 binding by phospholipase A2

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:5564302

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

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

Phospholipase A2 (PLA2) treatment has been shown previously to stimulate the sodium-dependent high-affinity choline uptake system as assessed by both the specific binding of (3H)hemicholinium-3 (( 3H)HCh-3) and the uptake of (3H)choline. In the present study, the specificity of PLA2-induced stimulation upon (3H)HCh-3 binding has been examined. PLA2, as well as phospholipase C (PLC), treatment of synaptic membranes produced a dose-dependent increase in the specific binding of (3H)HCh-3 whereas neither phospholipase B nor phospholipase D had any effect. PLC-induced stimulation of (3H)HCh-3 binding resulted from a significant decrease in the Kd without a change in the maximum binding of (3H)HCh-3 binding. PLC treatment of synaptosomes resulted in an inhibition of (3H)choline uptake accompanied by an inhibition of Na+, K+-adenosine triphosphatase activity. In contrast to the increase of (3H)HCh-3 binding, the specific binding of both (3H)desipramine and (3H)mazindol was decreased by PLA2 treatment. After PLA2 treatment, (3H)HCh-3 binding was increased about 2.5-fold over basal levels in different regions of the brain. Electrolytic lesions of the medial septal nucleus and kainic acid-induced lesions of the striatum resulted in a marked reduction of (3H)HCh-3 binding in the hippocampus and the striatum, respectively. Residual (3H)HCh-3 binding in the denervated hippocampus and lesioned striatum was increased by PLA2 treatment but remained lower than that in PLA2-treated controls. Finally, atropine-induced up-regulation of (3H)HCh-3 binding in vivo was not additive with PLA2-induced stimulation. These results support the hypothesis that PLA2 might be involved in the regulation of the sodium-dependent high-affinity choline uptake.

• OSTI ID: 5564302
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 249:3; ISSN 0022-3565; ISSN JPETA
• 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
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHOLINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ESTERS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LIPASE
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
SPECIFICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES