Interaction of viral infections with muscarinic receptors

Both in humans and in experimental animals, much of the airway hyperresponsiveness that accompanies vital infections is the result of increased reflex bronchoconstriction. The M₃ muscarinic receptors on the airway smooth muscle function normally during vital infections so that the direct effects of acetylcholine on the smooth muscle are not altered. In contrast, the M₂ muscarinic receptors on the vagal nerve endings, which normally inhibit acetycholine release, are markedly dysfunctional during viral infections. This leads to substantial increases in acetylcholine release and potentiated reflex bronchoconstriction. Multiple mechanisms account for virus-induced M₂ receptor dysfunction. Vital neuraminidase may deglycosylate the M₂ receptor, decreasing acetylcholine affinity. Furthermore, both viruses and interferon-γ decrease M₂ receptor gene expression. Finally, in atopic hosts, vital infection causes M₂ receptor dysfunction by activating eosinophils, causing them to release major basic protein which binds to the M₂ receptor, functioning as an endogenous antagonist.