Effects of neuraminidase on airway reactivity in the guinea pig.
We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.
Département de Physiologie, Service de Pharmacologie Clinique, Créteil, France.
P H
PH
Jarreau
A
A
Harf
M
M
Levame
C R
CR
Lambré
H
H
Lorino
I
I
Macquin-Mavier
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000209:etiology; D001985:Bronchial Provocation Tests; D006168:Guinea Pigs; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D009439:Neuraminidase / Q000302:isolation & purification / Q000494:pharmacology*; D009976:Orthomyxoviridae Infections / Q000150:complications; D018184:Paramyxoviridae Infections / Q000150:complications; D013373:Substance P / Q000494:pharmacology; D014734:Vibrio cholerae / Q000201:enzymology
D013373:Substance P; D009439:Neuraminidase; D015260:Neprilysin; D000420:Albuterol