Am. J. Respir. Crit. Care Med., Vol 149, No. 5, May 1994, 1175-1179.
Capsaicin-induced airway obstruction in tracheally perfused guinea pig lungs
CM Lilly, G Besson, E Israel, IW Rodger and JM Drazen
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
The neurokinin receptors responsible for transducing the airway obstruction
resulting from capsaicin infusion were defined in the tracheally perfused
guinea pig lung. In this lung preparation, buffer is perfused via the
trachea and allowed to exit the lung through numerous small holes in the
pleural surface; airway obstruction is monitored as the backpressure (Pao)
generated at a constant perfusion flow rate. Infusion of the specific NK1
receptor agonist, Sar-9 Met02(11) substance P, resulted in an increase in
Pao; this effect was prevented by the NK1 receptor antagonist CP 99,994 but
not by the NK2 receptor antagonist SR 48,968. Infusion of the specific NK2
receptor agonist Nle10-neurokinin A 4-10 resulted in an increase in Pao;
this effect was prevented by the NK2 receptor antagonist SR 48,968 but not
by the NK1 receptor antagonist CP 99,994. In the absence of NK receptor
antagonists, infusion of capsaicin resulted in a significant increase in
Pao, 31 +/- 4 cm H2O. In the presence of the NK1 receptor antagonist, the
capsaicin response was not diminished, but in the presence of the NK2
receptor antagonist, the Pao response diminished to only 10 +/- 2 cm H2O, p
< 0.001. These data indicate that when capsaicin is presented to the
epithelial surface of the lung the resulting airway obstruction is mediated
predominantly by NK2 receptor stimulation.
