OKY-046 inhibits anaphylactic bronchoconstriction and reduces histamine level in bronchoalveolar lavage fluid in sensitized guinea pigs

1990 ◽  
Vol 39 (6) ◽  
pp. 623-637 ◽  
Author(s):  
F. Nambu ◽  
S. Murakata ◽  
T. Shiraji ◽  
N. Omawari ◽  
M. Sawada ◽  
...  
1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.


1992 ◽  
Vol 4 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Jerry W. Highfill ◽  
Gary E. Hatch ◽  
Ralph Slade ◽  
Kay M. Crissrnan ◽  
Joel Norwood ◽  
...  

Respirology ◽  
2007 ◽  
Vol 12 (6) ◽  
pp. 828-833
Author(s):  
Miki ABO ◽  
Kazuyoshi KURASHIMA ◽  
Masaki FUJIMURA ◽  
Shigeharu MYOU ◽  
Shinji NAKAO ◽  
...  

1990 ◽  
Vol 16 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Jacques Rami ◽  
Laurent Brondel ◽  
Daniel Rivière ◽  
Jean-Paul Besombes

2015 ◽  
Vol 5 (1) ◽  
pp. 12-19
Author(s):  
Nirmathan Tharmalingam ◽  
I. Medvedova ◽  
A. Eichlerova ◽  
M. Prso ◽  
D. Mokra ◽  
...  

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.


Sign in / Sign up

Export Citation Format

Share Document