Influence of the thr164ile polymorphism in the β 2-adrenoceptor on the effects of β-adrenoceptor agonists on human lung mast cells

Abstract

We have examined the influence of the thr164ile polymorphism in the β 2-adrenoceptor on the ability of the β-adrenoceptor agonists, isoprenaline and salbutamol, to stabilise human lung mast cells. A total of 124 mast cell preparations were genotyped and, of these, 120 were found to be homozygous (thr164thr) at position 164 of the β 2-adrenoceptor and 4 were heterozygous (thr164ile). None of the preparations was homozygous for ile at position 164. In these preparations, the effects of isoprenaline and salbutamol on the IgE-mediated release of histamine from mast cells were studied. Both isoprenaline and salbutamol inhibited histamine release in a concentration-dependent manner. Average inhibitory potencies for both agonists, as assessed by p D 2 values, were higher in homozygous than in heterozygous preparations. For isoprenaline, this difference was statistically significant ( P<0.005), whereas for salbutamol, it was not ( P=0.21). These data suggest that the thr164ile polymorphism in the β 2-adrenoceptor may influence the extent to which certain β-adrenoceptor agonists inhibit the responses of mast cells.