title: The effect of beta2-adrenoceptor agonists on phospholipase C (beta1) signalling in human airway smooth muscle cells.
abstract: Prolonged use of beta2-adrenoceptor agonists has been associated with asthma exacerbation. Recently, phospholipase C-beta1 (PLC-beta1) induction in airway smooth muscle was proposed to underlie this phenomenon. We aimed to evaluate this mechanism in primary human airway smooth muscle cells. Stimulation of cells (1 microM isoprenaline or salbutamol for 2-48 h or 10(-9)-10(-4)M for 24 h) had no effect on PLC-beta1 gene expression. 1 microM beta2-adrenoceptor agonist treatment for 24 h did not alter sodium fluoride Inositol Phosphate (IP) responses, however augmented histamine IP responses (P<0.05). Therefore, beta2-adrenoceptor agonists can augment spasmogen responses in airway smooth muscle but not via a G-protein/PLC-beta1 mediated mechanism.
authors.affiliation: Division of Therapeutics and Molecular Medicine, University Hospital of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Sayers
authors.forename: Caroline
authors.initials: C
authors.lastname: Swan
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D007295:Inositol Phosphates; D007527:Isoenzymes; D018343:Receptors, Adrenergic, beta-2; D006632:Histamine; D012969:Sodium Fluoride; D010738:Type C Phospholipases; D007545:Isoproterenol; D000420:Albuterol