Parainfluenza virus type 1 reduces the affinity of agonists for muscarinic receptors in guinea-pig lung and heart.
Membrane preparations of guinea-pig lung (containing multiple muscarinic receptor subtypes) and heart (containing M2 receptors only) were incubated with either neuraminidase, parainfluenza virus (which contains neuraminidase), or virus plus 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, a neuraminidase inhibitor. None of these treatments affected [3H]quinuclidinyl benzilate [( 3H]QNB) binding. In the lung and heart, carbachol displaced 0.2 nM [3H]QNB from two sites. After treatment with either neuraminidase or virus the high affinity site was shifted to the right, and carbachol displaced QNB from one site with low affinity in the lung. In contrast, neuraminidase or virus decreased the affinity of carbachol for both sites in the heart. The neuraminidase inhibitor completely blocked virus-induced changes in carbachol affinity in both tissues. These results suggest that parainfluenza virus decreases the affinity of agonists for some of the muscarinic receptors in the lung, and for all of the muscarinic receptors in the heart due to its neuraminidase activity, which results in removal of sialic acid. The decreased agonist affinity in the lung may be responsible for the increased vagally induced bronchoconstriction seen in viral respiratory infections.
Fryer
A D
AD
Department of Pharmacology and Toxicology, School of Pharmacy, University of Maryland, Baltimore 21201.
el-Fakahany
E E
EE
Jacoby
D B
DB
D000818:Animals; D002217:Carbachol / Q000378:metabolism; D002478:Cells, Cultured; D006168:Guinea Pigs; D006389:Hemagglutinins, Viral / Q000032:analysis; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010222:Parainfluenza Virus 1, Human / Q000201:enzymology / Q000378:metabolism*; D018184:Paramyxoviridae Infections / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012794:Sialic Acids / Q000494:pharmacology
D006389:Hemagglutinins, Viral; D011976:Receptors, Muscarinic; D012794:Sialic Acids; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid