Pharmacological characterisation of the β-adrenoceptor expressed by human lung mast cells

The nonselective β-adrenoceptor agonist, isoprenaline (pD₂; 8.8±0.2), and selective β₂-adrenoceptor agonists, clenbuterol (9.2±0.4) and salbutamol (7.1±0.1), inhibited the immunoglobulin E-mediated release of histamine from human lung mast cells in a concentration-dependent manner. The β₂-adrenoceptor-selective antagonist, ICI118551 (erythro-(±)-1-(7-methylindan-4-yloyl)-3-isopropylaminobutan-2-ol HCl), antagonised the isoprenaline inhibition of histamine release from human lung mast cells with high affinity (apparent pK_B; 9.5±0.2), whereas high concentrations of the β₁-adrenoceptor-selective antagonist, CGP20712A (2-hydroxy-5-(2-(hydroxy-3-(4((1-methyl-4-trifluoromethyl)-1-H- imidazol-2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide), were required to reverse the isoprenaline inhibition (apparent pK_B; 6.5±0.3). Radioligand binding studies using [¹²⁵I]-iodocyanopindolol ([¹²⁵I]CYP) were performed on membranes derived from purified mast cells (>90% purity). Binding of [¹²⁵I]CYP to mast cell membranes was displaced from a single binding site with a high affinity for ICI118551 (pK_i; 8.9±0.1) and low affinity for CGP20712A (pK_i; 6.0±0.03), indicative of a homogeneous population of β₂-adrenoceptors. In contrast, in human lung membranes, these antagonists displaced [¹²⁵I]CYP from two sites indicative of a heterogeneous population of β₁-adrenoceptors (20%) and β₂-adrenoceptors (80%). These data indicate that the β-adrenoceptor expressed by human lung mast cells and mediating inhibition of mediator release from these cells is the β₂-adrenoceptor.