Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung.
1. The effects of salmeterol, a novel long-acting beta 2-adrenoceptor agonist, have been investigated on antigen-induced mediator release from passively sensitized fragments of human lung in vitro. 2. Salmeterol was a potent inhibitor of the release of histamine (-log IC50 = 8.54), leukotriene C4 (LTC4)/LTD4 (-log IC50 = 9.07) and prostaglandin D2 (-log IC50 = 8.81). It was slightly less potent (1-3 fold) than isoprenaline, but significantly more potent (10-35 fold) than salbutamol. 3. Propranolol competitively antagonized the inhibitory effects of salmeterol on histamine release (pA2 = 8.41) and LTC4/LTD4 release, (pA2 = 8.40) indicating an action via beta-adrenoceptors. 4. The inhibitory effects of isoprenaline (20 nM) and salbutamol (200 nM) were removed after washing the lung tissue for 2 h and 4 h respectively. In contrast, the inhibitory effects of salmeterol (40 nM) were much longer-lasting, and were still evident after 20 h. 5. Salmeterol therefore exhibits potent and persistent inhibition of anaphylactic mediator release from human lung. This anti-inflammatory effect may be important for the therapeutic potential of salmeterol in the treatment of bronchial asthma.
Butchers
P R
PR
Department of Peripheral Pharmacology, Glaxo Group Research, Ware, Herts.
Vardey
C J
CJ
Johnson
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D013189:SRS-A; D000068299:Salmeterol Xinafoate; D011433:Propranolol; D000420:Albuterol; D015230:Prostaglandin D2