Attenuating effect of H+K+ATPase inhibitors on airway cough hypersensitivity induced by allergic airway inflammation in guinea-pigs.
BACKGROUND
Gastrooesophageal reflux (GER) is a frequent cause of chronic cough. Several investigators have indicated that inhibitors of H(+)K(+)ATPase (proton pump inhibitors; PPIs) could relieve coughing via inhibition of acid reflux. However, we considered that PPIs might directly inhibit increased cough reflex sensitivity.


OBJECTIVE
The present study was designed to examine whether PPIs directly inhibit antigen-induced increase in cough reflex sensitivity and to elucidate the mechanism.


METHODS
Actively sensitized guinea-pigs were challenged with aerosol antigen (ovalbumin, OVA) and cough reflex sensitivity to inhaled capsaicin was measured 24 h later. The PPIs (omeprazole and rabeprazole) or the histamine H(2) blocker cimetidine were administered intraperitoneally 1 h before OVA challenge and before measuring cough reflex sensitivity, then bronchoalveolar lavage fluid (BALF) was immediately collected. The pH of the fluid obtained by bronchial washing was determined after examining the effect of rabeprazole on the cough response to capsaicin.


RESULTS
The number of coughs elicited by capsaicin was significantly increased 24 h after challenge with OVA compared with saline, indicating antigen-induced increase in cough reflex sensitivity. Both PPIs dose dependently and significantly inhibited antigen-induced cough hypersensitivity. Omeprazole did not influence the antigen-induced increase in the total number of cells or ratio (%) of eosinophils in BALF. Cimetidine did not affect the antigen-induced cough hypersensitivity or cellular components of BALF. The pH of the bronchial washing fluid was significantly decreased in antigen-challenged animals. Rabeprazole did not affect the antigen-induced decrease in the pH of bronchial washing fluid.


CONCLUSIONS
These findings show that PPIs, but not histamine H(2) blockers, can directly decrease antigen-induced cough reflex hypersensitivity, while the mechanism remains unclear.
Oribe
Y
Y
Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa 920, Japan. oribe@s8.dion.ne.jp
Fujimura
M
M
Kita
T
T
Katayama
N
N
Nishitsuji
M
M
Hara
J
J
Myou
S
S
Nakao
S
S
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000485:Allergens; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001980:Bronchi / Q000737:chemistry; D001992:Bronchoalveolar Lavage Fluid; D002211:Capsaicin; D002927:Cimetidine / Q000627:therapeutic use; D003371:Cough / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D017506:H(+)-K(+)-Exchanging ATPase / Q000032:analysis; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D007509:Irritants; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010047:Ovalbumin; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D014132:Trachea / Q000737:chemistry
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000485:Allergens; D001562:Benzimidazoles; D006635:Histamine H2 Antagonists; D007509:Irritants; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D002927:Cimetidine; D010047:Ovalbumin; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D002211:Capsaicin