Figure 5.

Determining the role of transient receptor potential channel A1 (TRPA1) and TRPV1 in prostaglandin E₂ (PGE₂) and bradykinin (BK)-induced cough in conscious guinea pigs. (A) Capsaicin and (B) acrolein concentration-dependently induced coughing in conscious, unrestrained guinea pigs. Tussive agents were aerosolised for 5 min, the number of coughs was counted during this time and for a further 5 min post stimulation (10 min total). Data are presented as mean ± SEM of n=10–12 observations. (C, D) Animals received intraperitoneal injections with a concentration of TRPA1 antagonist HC-030031 (HC), TRPV1 antagonist JNJ17203212 (JNJ) or vehicle (Veh) 1 h prior to 5 min aerosol stimulation with a tussive agonist. The number of coughs was counted during the 5 min stimulation plus a further 5 min (10 min total). (C) HC concentration-dependently inhibited acrolein-induced coughing (100 mM; open circles), but had no effect on capsaicin cough (60 μM; filled circles) at 300 mg/kg. (D) Conversely, JNJ concentration-dependently inhibited capsaicin-induced cough, with no effect on acrolein at 100 mg/kg. Data are presented as mean ± SEM of n=8–10 observations. (E, F) Animals received intraperitoneal injection with HC (300 mg/kg; filled circles), JNJ (100 mg/kg; filled squares), a combination of both antagonists (HC+JNJ; filled triangles), or appropriate Veh (open circles) 1 h prior to stimulation with a tussive agonist. (E) PGE₂ (300 μg/ml) or (F) BK (3 mg/ml) were aerosolised for 10 min, during which time the number of coughs was counted. Compared with vehicle control, pretreatment with either HC or JNJ significantly inhibited PGE₂-induced or BK-induced coughing; and pr-treatment with HC+JNJ abolished cough altogether. Data are presented as median ± IQR of n=10–12 observations. *(p<0.05), **(p<0.01) and ***(p<0.0001) indicate statistical significance, Kruskal–Wallis one-way analysis of variance with Dunn's multiple comparison post-test.