Neurokinin-1 receptor antagonist inhibits short-term sulfuric-acid-induced airway hyperresponsiveness in sensitized guinea pigs.
BACKGROUND
Tachykinins are involved in the development of bronchial inflammation and airway hyperresponsiveness (AHR); however, the role of the neurokinin-1 (NK(1)) receptor in acid-aerosol-induced bronchial impairment in asthmatic patients remains controversial.


METHODS
To investigate the effects on the NK(1) receptor antagonist FK888 the neurokinin-2 (NK(2)) receptor antagonist SR48968 on sulfuric-acid (H(2)SO(4))-induced AHR in guinea pigs, specific airways resistance (sRaw) and airways responsiveness to methacholine (MCh) were measured before and after 6 h of exposure to H(2)SO(4) aerosol (pH 1.7, 82 mg/m(3)) in ovalbumin-sensitized guinea pigs.


RESULTS
Airway responsiveness to MCh significantly increased (p<0. 05) after the exposure, however sRaw did not. Treatment with FK888 significantly inhibited (p<0.05) H(2)SO(4)-induced AHR in a dose-dependent manner, as did SR48968.


CONCLUSIONS
These results suggest that not only NK(2) but also NK(1) receptors might have important roles in the development of acid-aerosol-induced AHR.
Teramoto
S
S
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tanaka
H
H
Kaneko
S
S
Abe
S
S
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride; D009330:Nebulizers and Vaporizers; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000276:immunology*; D010880:Piperidines / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013464:Sulfuric Acids / Q000009:adverse effects*
D000336:Aerosols; D001549:Benzamides; D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D013464:Sulfuric Acids; D016210:Methacholine Chloride; C078949:FK 888; C073839:SR 48968; D010047:Ovalbumin; C033158:sulfuric acid