Inhibitory actions of salmeterol on human airway macrophages and blood monocytes.
The effect of beta 2-adrenoceptor agonists, salmeterol and salbutamol on thromboxane B2 release from human airway macrophages and peripheral blood monocytes has been examined. Salbutamol (0.1-100 microM) had no inhibitory effect on the release of thromboxane B2 from human airway macrophages. Salmeterol (0.1-100 microM) caused dose-dependent inhibition of thromboxane B2 release from human airway macrophages stimulated by either zymosan or calcium ionophore A23187. This inhibition was not blocked by propranolol (1 microM). The activity of adenylyl cyclase in homogenates of human airway macrophages was increased by NaF (10 mM) by 8.5-fold and salmeterol (100 microM) and isoprenaline (10 microM) by 1.6- and 1.4-fold, respectively. Isoprenaline alone was inhibited by propranolol (1 microM). Salmeterol caused a biphasic inhibition of peripheral blood monocyte thromboxane B2 release. The inhibition at low (10 nM) concentrations of salmeterol was blocked by propranolol and that at higher concentrations (100 microM) was unaffected. The long lipophilic tail of salmeterol had similar inhibitory effects on the airway macrophages to salmeterol itself, and on the peripheral blood monocytes its action resembled that of the highest concentrations of salmeterol used. It is concluded that salmeterol inhibits mediator release from human airway macrophages by a beta-adrenoceptor independent mechanism and from blood monocytes by both beta-adrenoceptor and non-beta-adrenoceptor mechanisms. The latter mechanism may be associated with the lipophilic properties of the salmeterol molecule.
Baker
A J
AJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Palmer
J
J
Johnson
M
M
Fuller
R W
RW
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D000068299:Salmeterol Xinafoate; D012969:Sodium Fluoride / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000001:Calcimycin; D013929:Thromboxane B2; D000068299:Salmeterol Xinafoate; D012969:Sodium Fluoride; D015054:Zymosan; D011433:Propranolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000420:Albuterol