We examined the effect of inhaled
ATP on the chemical
irritant-induced
coughs to clarify the roles of ionotropic
purinergic receptors in these modulations. Although inhalation of 0.1 M
citric acid by itself produced only a few
coughs in guinea pigs, exposure to
ATP, at concentrations of 3-10 microM, for 2 min concentration-dependently increased the number of 0.1 M
citric acid-induced
coughs.
ATP-induced enhancement of the number of
citric acid-induced
coughs was abolished when animals were pretreated with 2',3'-O-(2,4,6-trinitrophenyl)
adenosine 5-triphosphate (
TNP-ATP), an antagonist of P2X receptor subtypes P2X1-4, at a concentration of 50 microM, for 2 min. However, exposure to pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic
acid (
PPADS), an antagonist of P2X receptor subtypes P2X1,2,3,5,7, but not of P2X4 receptors, at a concentration of 50 microM, for 2 min, had no effect on the
ATP-induced enhancement of the number of
citric acid-induced
coughs. Furthermore, exposure to
reactive blue 2 (RB2, 30 microM, 2 min), an antagonist of P2Y receptors, had no effect on the
ATP-induced enhancement of the number of
citric acid-induced
coughs. Exposure to
ATP, at a concentration of 10 microM, for 2 min significantly increased the number of
citric acid-induced
coughs in
capsaicin-pretreated guinea pigs. Furthermore,
ATP had no effect on the number of
capsaicin-induced
coughs in naive animals. These results suggest that although
ATP, by itself, does not elicit spontaneous
coughs, it likely enhances the
cough reflex sensitivity. Furthermore, stimulation of P2X receptors, especially P2X4 receptors, on rapidly adapting receptors may be required for the
ATP-induced enhancement of the
cough reflex sensitivity.