Elsevier

Brain Research

Volume 723, Issues 1–2, 3 June 1996, Pages 90-99
Brain Research

Choline's phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons

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Abstract

The mechanism by which populations of brain cells regulate the flux of choline (Ch) into membrane or neurotransmitter biosynthesis was investigated using electrically stimulated superfused slices of rat corpus striatum. [Me-14C]Ch placed in the superfusion medium for 30 min during a 1-h stimulation period was incorporated into tissue [14C]phosphorylcholine (PCh) and [14C]phosphatidylcholine (PtdCh). Stimulation also caused a profound inhibition of PCh synthesis and a 10-fold increase in [14C]ACh release into the medium; it failed to affect tissue [14C]ACh levels. This effect was not explained by changes in ATP levels nor in the kinetic properties of Ch kinase (E.C. 2.7.1.32) or Ch acetyltransferase (ChAT) (E.C. 2.3.1.7). To investigate the mechanism of these effects, Ch uptake studies were performed with and without hemicholinium-3 (HC3), a selective inhibitor of high affinity Ch uptake. A two-compartment model accurately fit the observed data and yielded aKm for Ch uptake of 5 μM into cholinergic structures and 72 μM into all other cells. Using this model it was estimated that cholinergic neurons account for 60% of observed uptake of Ch at physiologic Ch concentrations, even though they represent fewer than 1 % of the total cells in the slice. The model also predicts that an increase in Ch uptake within cholinergic neurons, reported to be associated with depolarization [4,27,32], would significantly inhibit Ch uptake into all other cells, and would account for the observed decrease in PCh synthesis.

Keywords

Acetylcholine
Choline
Choline uptake
Phosphatidylcholine
Phosphocholine
Phospholipid
Choline acetyltransferase
Choline kinase
Rat striatum

Cited by (0)

1

Present address: Carnegie Institution of Washington, Department of Embryology, 115 West University Parkway, Baltimore, MD 21210, USA.

2

Present address: Department of Pathology, Boston University, Room M 1009, 85 E. Newton Street, Boston, MA 02118, USA.