Effects of leukotriene B 4 receptor antagonist, LY293111Na, on antigen-induced bronchial hyperresponsiveness and leukocyte infiltration in sensitized guinea pigs

2001 ◽  
Vol 50 (3) ◽  
pp. 136-141 ◽  
Author(s):  
F. Asanuma ◽  
K. Kuwabara ◽  
A. Arimura ◽  
Y. Furue ◽  
J.H. Fleisch ◽  
...  
1989 ◽  
Vol 66 (4) ◽  
pp. 1838-1845 ◽  
Author(s):  
G. D. Leikauf ◽  
C. A. Doupnik ◽  
L. M. Leming ◽  
H. E. Wey

The sulfidopeptide leukotrienes are bronchoconstrictive lipid mediators thought to have an important role in the pathophysiology of asthma. The objective of this study was to determine if treatment with a leukotriene receptor antagonist and 5-lipoxygenase inhibitors could diminish acrolein-induced bronchial hyperresponsiveness and to determine whether leukotriene (LT) C4 generation is augmented by acrolein exposure. Guinea pigs (groups of 6–7) were exposed to 1.3 ppm acrolein for 2 h and bronchial responsiveness to intravenous acetylcholine determined twice before, and once 1, 2, 6, and 24 h after exposure. Immediately after acrolein exposure (5 min) specific total airway resistance (sRt) increased from 0.86 +/- 0.01 to 1.29 +/- 0.07 ml.cmH2O.ml-1.s. Within 1 h after exposure, the effective dose of acetylcholine sufficient to double sRt (ED200) decreased from 114.0 +/- 6.6 to 58.5 +/- 6.5 micrograms.kg-1.min-1. Bronchial hyperresponsiveness became maximal at 2 h with ED200 = 44.7 +/- 4.2 and persisted for up to 24 h after exposure (24 h ED200 = 60.2 +/- 11.6 micrograms.kg-1.min). A LTC4/LTD4 receptor antagonist, L-649,923 (10 mg/kg iv), and two putative inhibitors of 5-lipoxygenase, L-651,392 (10 mg/kg po) and U-60,257 (5 mg/kg i.v.), diminished the immediate bronchoconstriction and markedly inhibited bronchial hyperresponsiveness. Analysis of bronchoalveolar lavage fluid obtained from guinea pigs after acrolein exposure revealed a significant increase in immunoreactive LTC4 concentrations (control LTC4 = 8.8 +/- 0.3, n = 7; exposed LTC4 = 15.9 +/- 2.4 pg/ml, n = 6). Treatment with L-651,392 inhibited this response (acrolein exposed = 9.4 +/- 2.4 pg/ml, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)


2003 ◽  
Vol 285 (2) ◽  
pp. G389-G395 ◽  
Author(s):  
Hidehiko Shimatani ◽  
Yu Kojima ◽  
Makoto Kadowaki ◽  
Tadashi Nakagawa ◽  
Hisao Fujii ◽  
...  

The rectal distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations in guinea pigs were generated through the extrinsic sacral excitatory nerve pathway (pelvic nerves) and the intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The aim of the present study was to evaluate whether a prokinetic benzamide, mosapride, enhances the R-R and R-IAS reflexes mediated via 5-HT4 receptors in the guinea pig. The mechanical activities of the R and IAS were recorded with a balloon connected to a pressure transducer and a strain gauge force transducer in the anesthetized guinea pig with intact spinal-intestinal pathways. Gradual and sustained rectal distension evoked R-R contractions and synchronous R-IAS relaxations. Mosapride (0.1–1.0 mg/kg iv) dose-dependently enhanced both R-R and R-IAS reflex responses. Reflex indexes for R-R and R-IAS maximally increased from 1.0 (control) to 1.92 and 1.88, respectively. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg iv), antagonized the enhancement of the R-R and R-IAS reflexes induced by mosapride 1.0 mg/kg iv. The present results indicate that mosapride enhanced the R-R and R-IAS reflexes mediated through 5-HT4 receptors.


1998 ◽  
Vol 47 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Shigenori Iwamae ◽  
Hideo Tsukagoshi ◽  
Takeshi Hisada ◽  
Daisuke Uno ◽  
Masatomo Mori

Life Sciences ◽  
1997 ◽  
Vol 60 (18) ◽  
pp. 1553-1561 ◽  
Author(s):  
Lee A. Phebus ◽  
Kirk W. Johnson ◽  
Peter W. Stengel ◽  
Karen L. Lobb ◽  
James A. Nixon ◽  
...  

1994 ◽  
Vol 65 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Shiro Shirakura ◽  
Katsuya Higo ◽  
Masami Takeda ◽  
Akira Karasawa

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