Muscarinic Mobilization of Choline in Rat Brain In Vivo as Shown by the Cerebral Arterio‐Venous Difference of Choline

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Abstract
In anesthetized rats, the choline levels of cerebrospinal fluid and plasma obtained from blood collected from peripheral vessels (carotid artery, cardiac vessels) and from the transverse sinus were determined with a radioenzymatic assay. Cortical release of choline was studied using the “cup technique.” The plasma choline level of the peripheral blood (11.5 μmol/L) was lower than that of the sinus blood. The resulting cerebral arterio-venous difference of choline was negative (3.2 μmol/L) and reflected the net release of choline from the whole brain. The plasma choline levels were not different irrespective of whether the rats were anesthetized with ether, urethane, or pentobarbital. However, the choline level of the cerebrospinal fluid, which normally was lower than the plasma choline levels, was increased by urethane anesthesia to a level between the arterial and venous plasma concentrations of the brain. In old rats (24 months), the choline level of the cerebrospinal fluid was significantly lowered, when compared with the results obtained with younger rats (2–4 months). In rats kept on a low-choline diet for 2 weeks, the plasma choline level of the peripheral blood was reduced to 51% of the control. The effect on the choline level of the sinus blood was smaller; the cerebral arterio-venous difference of choline was not reduced (it was even slightly enhanced). Likewise, the cholinelevel of the cerebrospinal fluid and the cortical release of choline were not altered. Intraperitoneal administration of oxotremorine in pentobarbital-anesthetized rats kept on a low-choline diet increased the plasma levels of choline. The rise of the plasma level of the peripheral blood was blocked by atropine and by methylatropine. Atropine alone or in combination with oxotremorine reduced the arterio-venous difference to half the level obtained by oxotremorine or oxotremorine plus methylatropine. In conclusion, the net formation of choline in the whole brain is partially controlled by central cholinergic activity and is unaltered even at a considerably reduced supply of choline from the peripheral circulation. Moreover, the remarkable maintenance of a certain choline level of the cerebrospinal fluid at a reduced (low-choline diet) or elevated (oxotremorine) plasma level also suggests that the extracellular concentration of choline in the brain is held at a constant level eventually at the expense of cellular phospholipids.