Modulation of DNA synthesis by muscarinic cholinergic receptors

Acetylcholine muscarinic receptors are a family of five G-protein-coupled receptors widely distributed in the central nervous system and in peripheral organs. Activation of certain subtypes of muscarinic receptors (M-1, M-3, M-5) has been found to modulate DNA synthesis in a number of cell types. In several cell types acetylcholine, by activating endogenous or transfected muscarinic receptors, can indeed elicit cell proliferation. In other cell types, however, or under different experimental conditions, activation of muscarinic receptors has no effect, or inhibits DNA synthesis. A large number of intracellular pathways are being investigated to define the mechanisms involved in these effects of muscarinic receptors; these include among others, phospholipase D, protein kinases C and mitogen-activated-protein kinases. The ability of acetylcholine to modulate DNA synthesis through muscarinic receptors may be relevant in the context of brain development and neoplastic growth.