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

The nonselective beta-adrenoceptor agonist, isoprenaline (pD(2); 8.8 +/- 0.2), and selective beta(2)-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 beta(2)-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 pKB; 9.5 0.2), whereas high concentrations of the beta(1)-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 pKB; 6.5 +/- 0.3). Radioligand binding studies using [I-125]-iodocyanopindolol ([I-125]Cyp) were performed on membranes derived from purified mast cells (>90% purity). Binding of [I-125]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 CGP20712AL (pK(i); 6.0 +/- 0.03), indicative of a homogeneous population beta(2)-adrenoceptors. In contrast, in human lung membranes, these antagonists displaced [1251]Cyp from two sites indicative of a heterogeneous population of beta(1)-adrenoceptors (20%) and beta(2)-adrenoceptors (80%). These data indicate that the beta-adrenoceptor expressed by human lung mast cells and mediating inhibition of mediator release from these cells is the beta(2)-adrenoceptor. (C) 2002 Elsevier Science B.V. All rights reserved.