Control of histamine induced inositol phospholipid hydrolysis in cultured human tracheal smooth muscle cells.
[3H]Inositol phosphate responses to histamine and a range of other agonists were studied in cultured human tracheal smooth muscle cells. Histamine (EC50 6.5 microM), bradykinin (EC50 9.7 nM), carbachol (EC50 10 microM), substance P and NaF all produced concentration dependent [3H]inositol phosphate formation in these cells. The response to histamine was inhibited by mepyramine (KA 4.3 x 10(9) M-1), indicating the involvement of the histamine H1 receptor in this response. The inositol phosphate response to histamine was apparently desensitized following prolonged agonist exposure. The response to histamine was inhibited by phorbol dibutyrate (IC50 6 nM), and this inhibitory effect was reversed by staurosporine (150 nM). Isoprenaline (1 microM), rolipram (0.1-100 microM) and 3-isobutyl-1-methylxanthine (0.1 mM) all produced small inhibitory effects upon histamine induced inositol phosphate formation. These results demonstrate that cultured human tracheal smooth muscle cells express histamine H1 receptors coupled to phosphoinositidase C and suggest that the inositol phosphate response induced by stimulation of this receptor subtype is inhibited by activation of protein kinase C and, to a lesser extent, by elevation of cell cyclic AMP content.
Department of Therapeutics, University Hospital of Nottingham, Queen's Medical Centre, UK.
K
K
Daykin
S
S
Widdop
I P
IP
Hall
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000096:biosynthesis / Q000187:drug effects; D020889:Rolipram; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D017442:Histamine Agonists; D007295:Inositol Phosphates; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D011969:Receptors, Histamine H1; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D000242:Cyclic AMP; D020889:Rolipram