Phosphoinositide metabolism in airway smooth muscle

Correlation of cyclic AMP accumulation and relaxant actions of salmeterol and salbutamol in bovine tracheal smooth muscle

“…One mechanism of potential significance is the ability of fl-adrenoceptor agonists (and other agents which increase cyclic AMP levels) to inhibit Hist-stimulated inositol phospholipid hydrolysis (Hall & Hill, 1988;Madison & Brown, 1988;Hall et al, 1989). These initial reports hypothesized that inhibition of inositol phospholipid turnover might be extrapolated to infer an effect on the concentration of inositol 1,4,5-trisphosphate, a second messenger generally acknowledged to be responsible for the initiation of pharmacomechanical coupling in airways smooth muscle (Chilvers et al, 1994a). Although more recent studies have not supported this idea (see Challiss et al, 1993), it is likely that the ability of f,-adrenoceptor agonists to inhibit a spasmogen-stimulated signal transduction pathway will contribute, to a greater or lesser degree, to the relaxant activity of these agents.…”

Regulation of histamine H1 receptor coupling by dexamethasone in human cultured airway smooth muscle

“…Histamine is an important contractile agonist for airway smooth muscle cells and is believed to initiate a contractile response in this tissue by stimulation of phospholipase C (Coburn & Baron, 1990;Chilvers & Hall, 1993). This results in an increase in the intracellular concentration of inositol 1,4,5 trisphosphate which in turn causes a rise in intracellular free calcium concentration by inducing calcium release from intracellular stores (Hashimoto et al, 1985).…”

“…We hypothesized that one mechanism through which corticosteroids may alter contractility of airway smooth muscle preparations is by altering the coupling of contractile agonist receptors to their intracellular signal transduction pathways in this tissue. Contractile agonists such as histamine and acetylcholine are believed to initiate a contractile response in airway smooth muscle via HI and M3 receptors respectively: these receptors are coupled in airway smooth muscle to phospholipase C (Hall & Hill, 1988;Meurs et al, 1989;Coburn & Baron, 1990;Chilvers & Hall, 1993). Stimulation of phospholipase C results in the formation of Author for correspondence.…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…It has been shown that histamine increases phosphoinositide metabolism (Hill, 1990) and IP 3 levels (Chilvers et al, 1994) via activation of phospholipase C by a pertussis toxin-insensitive G protein (Leurs et al, 1994). Rueda et al (2002) studied the Ca 2ϩ -dependence and wortmannin-sensitivity of the initial IP 3 response induced by activation of H 1 receptors in smooth muscle 598 ANDERSSON AND WEIN from guinea pig urinary bladder.…”