Influence of the thr164ile polymorphism in the beta2-adrenoceptor on the effects of beta-adrenoceptor agonists on human lung mast cells

We have examined the influence of the thr164ile polymorphism in the beta(2)-adrenoceptor on the ability of the beta-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 beta(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 pD(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 beta(2)-adrenoceptor may influence the extent to which certain beta-adrenoceptor agonists inhibit the responses of mast cells.