Regulation of free choline in rat brain: dietary and pharmacological manipulations.
The present study analyses, comparatively, the kinetics of free choline in the brain of rats during dietary and pharmacological manipulations. Low-choline diet halved the choline plasma level but did not cause significant changes of CSF choline. High-choline diet, hypoxia and treatment with nicotinamide increased brain choline availability through a central site of action and increased the CSF choline concentration. CSF choline concentrations were more effectively elevated by nicotinamide treatment (20-25 microM) than by acute choline administration (13-15 microM). Increases of CSF choline, due to brain choline mobilization, were consistently associated with a net release of choline from the brain as reflected by strongly negative arterio-venous differences (AVD) of brain choline. The balance between release and uptake of brain choline was controlled by the arterial plasma choline level in all treatment groups; however, the normal 'reversal point' of 15 microM--representing the plasma choline level where uptake and release of brain choline are balanced--was shifted to more than 40 microM by high-choline diet and nicotinamide. In conclusion, our data characterize the release of choline into the venous blood as an important component of brain choline homeostasis. Furthermore, we demonstrate that the concentration of brain choline (e.g. as a precursor of acetylcholine) can be enhanced more efficiently by manipulating choline homeostatic mechanisms than by acute choline administration.
Department of Pharmacology, University of Mainz, Germany.
J
J
Klein
A
A
Köppen
K
K
Löffelholz
D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002536:Cerebral Arteries; D002550:Cerebral Veins; D002794:Choline / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D004032:Diet; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar
D009536:Niacinamide; D002794:Choline