In addition to stimulating the metabolism of phosphoinositides, cholinergic muscarinic agonists have also been shown to activate hydrolysis of phosphatidylcholine by phospholipase D. This reaction, which yields phosphatidic acid (PA) and choline, has been identified in a number of in vitro cell preparation; however, several investigators failed to observe stimulation of phospholipase D activity by carbachol in hippocampal or cortical slices from adult rats. Here we report that carbachol causes activation of phospholipase D, measured by the formation of phosphatidylethanol (PEtOH) in the presence of ethanol, and of PA, in cortical slices from 7 day-old rats. The effect of carbachol was blocked by the muscarinic antagonist atropine but not by H7, an inhibitor of PKC, and was mimicked by glutamate and the phorbol ester TPA. Activation of phospholipase D by carbachol was also observed in rat cortical astrocytes in primary cultures. Differently from brain slices, PA formation in astrocytes appeared to totally derive from hydrolysis of phosphatidylcholine. Activation of phospholipase D by muscarinic agonists in brain from immature rats may play a relevant role in some developmental actions of acetylcholine such as, for example, its mitogenic effect in astrocytes.
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