Involvement of P2X receptor subtypes in ATP-induced enhancement of the cough reflex sensitivity.
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.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Takahashi
Yoshiki
Y
Yoshikawa
Yuji
Y
Saitoh
Akiyoshi
A
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D002211:Capsaicin; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D012018:Reflex; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism
D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D019343:Citric Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D002211:Capsaicin