Viral infection increases contractile but not secretory responses to substance P in ferret trachea.
Viral infection increases the airway smooth muscle response to substance P. This effect is due to decreased activity of neutral endopeptidase (EC 3.4.24.11), an enzyme that degrades substance P. Inhibition of neutral endopeptidase activity also potentiates substance P-induced 35SO4-labeled macromolecule secretion. Therefore we examined the in vitro effects of substance P on 35SO4-macromolecule secretion from the tracheae of influenza-infected ferrets. Despite a virus-induced loss of neutral endopeptidase activity (demonstrated in muscle bath experiments), there was no difference between control and infected tracheae in either baseline secretion [697 +/- 125 vs. 579 +/- 67 (SE) cpm/15 min; n = 15 tissues) or in the response to 10(-6) M substance P (increased by 218 +/- 63 and 195 +/- 51, respectively) or 10(-5) M substance P (increased by 416 +/- 95 and 354 +/- 54, respectively). Although phosphoramidon (10(-6) M) potentiated the secretory response to substance P, there was again no difference between control and infected tracheae. These data show that although viral infection decreases airway neutral endopeptidase activity, virus-induced hypersecretion is not due to a resulting increase in the secretory response to substance P.
Division of Pulmonary and Critical Care Medicine, University of Maryland, Baltimore 21201.
T C
TC
Murray
D B
DB
Jacoby
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005289:Ferrets; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D006020:Glycopeptides; D013373:Substance P; D015260:Neprilysin; D000109:Acetylcholine; C008890:phosphoramidon