title: Pharmacological characterisation of the beta-adrenoceptor expressed by human lung mast cells.
abstract: The nonselective beta-adrenoceptor agonist, isoprenaline (pD2; 8.8 +/- 0.2), and selective beta2-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 beta2-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 beta1-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 beta2-adrenoceptors. In contrast, in human lung membranes, these antagonists displaced [125I]CYP from two sites indicative of a heterogeneous population of beta1-adrenoceptors (20%) and beta2-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 beta2-adrenoceptor.
authors.affiliation: Section of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital (Floor L), Glossop Road, S10 2JF, Sheffield, UK.
authors.forename: Lee K
authors.initials: LK
authors.lastname: Chong
authors.forename: Russell
authors.initials: R
authors.lastname: Chess-Williams
authors.forename: Peter T
authors.initials: PT
authors.lastname: Peachell
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C049763:CGP 20712A; D007545:Isoproterenol