Effect of BRL-35135 on LTB4-induced guinea pig eosinophil chemotaxis.
The effect of an atypical beta-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 x 10(-6) and 2.6 x 10(-7) M, respectively). However, isoproterenol, fenoterol and another atypical beta-agonist, BRL-37344 had no effects. The inhibitory effect of BRL-35135 was not affected by (+/-)-propranolol (10(-4) M). In contrast, the nonselective beta-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 pA2 value of 5.62. These findings suggest that guinea pig eosinophils possess an "atypical receptor", which differs from either beta 1-, beta 2- or atypical beta-adrenoceptor on guinea pig ileum, and through which eosinophil chemotaxis can be modulated by BRL-35135.
Sugasawa
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Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Morooka
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D010627:Phenethylamines; D007975:Leukotriene B4; C057368:BRL 37344; D000526:Alprenolol; C063157:BRL 35135; D011433:Propranolol