Modulation of DNA synthesis by muscarinic cholinergic receptors

Acetylcholine muscarinic receptors are a family of five G-protein-coupled r eceptors 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 t ypes, however, or under different experimental conditions, activation of mu scarinic 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 othe rs, phospholipase D, protein kinases C and mitogen-activated-protein kinase s. The ability of acetylcholine to modulate DNA synthesis through muscarini c receptors may be relevant in the context of brain development and neoplas tic growth.