Interaction of viral infections with muscarinic receptors.
Both in humans and in experimental animals, much of the airway hyperresponsiveness that accompanies viral infections is the result of increased reflex bronchoconstriction. The M3 muscarinic receptors on the airway smooth muscle function normally during viral 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. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Furthermore, both viruses and interferon-gamma decrease M2 receptor gene expression. Finally, in atopic hosts, viral 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.
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
D B
DB
Jacoby
A D
AD
Fryer
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D016084:Bronchoconstriction / Q000502:physiology; D006801:Humans; D018184:Paramyxoviridae Infections / Q000378:metabolism* / Q000503:physiopathology; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000378:metabolism* / Q000503:physiopathology; D015320:Tachykinins / Q000502:physiology; D014630:Vagus Nerve / Q000378:metabolism
D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D015320:Tachykinins; D000109:Acetylcholine