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Effect of BRL-35135 on LTB4-induced guinea pig eosinophil chemotaxis

  • Allergy and Histamine
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Abstract

The effect of an atypical β-adrenoceptor agonist, BRL-35135 on leukotriene B4-induced-guinea pig eosinophil chemotaxis was studied. BRL-35135 and SC-41930 (leukotriene B4-antagonist) inhibited the chemotaxis in a concentration-dependent manner (IC50=9.0×10−6 and 2.6×10−7 M, respectively). However, isoproterenol, fenoterol and another atypical β-agonist, BRL-37344 had no effects. The inhibitory effect of BRL-35135 was not affected by (±)-propranolol (10−4 M). In contrast, the nonselective β-adrenoceptor antagonist, (−)-alprenolol (10−4 M) dextrally shifted the inhibitory curve of BRL-35135. The response to BRL-35135 was antagonized in a competitive manner by (−)-alprenolol, with the slope of the Schild plot close to unity, and a pA 2 value of 5.62. These findings suggest that guinea pig eosinophils possess an “atypical receptor”, which differs from eitherβ 1,β 2 or atypical β-adrenoceptor on guinea pig ileum, and through which eosinophil chemotaxis can be modulated by BRL-35135.

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Abbreviations

AR:

adrenoceptor

CR:

concentration ratio

EDTA:

ethylenediamine tetraacetic acid disodium salt

DNase 1:

deoxyribonuclease 1

HBSS:

Hanks' balanced salt solution

LTB4 :

leukotriene B4

IC50 :

50% inhibitory concentration

mHBSS:

modified HBSS

PBS:

Dulbecco's phosphate-buffered saline

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  1. Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., 1-98, Kasugade-Naka 3-Chome, Konohana-ku, 554, Osaka, Japan

    T. Sugasawa & S. Morooka

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  1. T. Sugasawa
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Sugasawa, T., Morooka, S. Effect of BRL-35135 on LTB4-induced guinea pig eosinophil chemotaxis. Agents and Actions 37, 232–237 (1992). https://doi.org/10.1007/BF02028114

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