CONTROL OF HISTAMINE-INDUCED INOSITOL PHOSPHOLIPID HYDROLYSIS IN CULTURED HUMAN TRACHEAL SMOOTH-MUSCLE CELLS

[H-3]Inositol phosphate responses to histamine and a range of other agonists were studied in cultured human tracheal smooth muscle cells. Histamine (EC50 6.5 muM), bradykinin (EC50 9.7 nM), carbachol (EC50 10 muM), substance P and NaF all produced concentration dependent [H-3]inositol phosphate formation in these cells. The response to histamine was inhibited by mepyramine (K(A) 4.3 x 10(9) M-1), indicating the involvement of the histamine H-1, 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 muM), rolipram (0.1-100 muM) 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 H-1 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.