Effects of inflammatory cells on neuronal M-2 muscarinic receptor functionin the lung

In the lungs, acetylcholine released from the parasympathetic nerves stimul ates M-3 muscarinic receptors on airway smooth muscle inducing contraction and bronchoconstriction. The amount of acetylcholine released from these ne rves is limited locally by neuronal M-2 muscarinic receptors. These neurona l receptors are dysfunctional in asthma and in animal models of asthma Decr eased M-2 muscarinic receptor function results in increased release of acet ylcholine and in airway hyperreactivity. Inflammation has long been associa ted with hyperreactivity and the role of inflammatory cells in loss of neur onal M-2 receptor function has been examined. There are several different m echanisms for loss of neuronal M-2 receptor function. These include blockad e by endogenous antagonists such as eosinophil major basic protein, decreas ed expression of M-2 receptors following infection with viruses or exposure to pro inflammatory cytokines such as gamma interferon. Finally, the affin ity of acetylcholine for these receptors can be decreased by exposure to ne uraminidase.