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.