Interaction of choline with muscarine receptor-stimulated phosphoinositide metabolism in the rat brain

Previous receptor binding studies had shown that choline can interact with low potency with muscarine cholinoceptors. In the present study we have investigated whether choline is capable of functionally activating muscarine receptors by investigating its ability in stimulating the hydrolysis of phosphoinositides, a response believed to be coupled in brain to the M1 subtype of muscarine receptors. The results indicated that choline was only a very weak inducer of inositol phosphates (InsPs) accumulation in rat cerebral cortex slices as compared with acetylcholine or charbachol. Maximal increase of InsPs accumulation, at a choline concentration of 10 mM, was only 39 +/- 7%, as compared with the 4- to 6-fold stimulation induced by the other compounds. This effect of choline was not modified by physostigmine nor by the uptake inhibitor hemicholinium-3. At high concentrations, however, choline antagonized the stimulatory effect of acetylcholine and carbachol, suggesting that it might act as a partial agonist at this subtype of muscarine receptors, similar to what has been observed with oxotremorine. Choline had no effect on noradrenaline-stimulated InsPs accumulation.