Signal transduction in smooth muscle cells from human airways.

The aim of this study deals with the post-receptor events involved in the response of cultured smooth muscle (SMC) from human bronchi to various agonists of the contraction. [3H]inositol phosphates (IPs) were isolated by high performance liquid chromatography (HPLC) and intracellular Ca2+ concentration ([Ca2+]i) was determined with the Fura-2 fluorescence technique. Following 5 sec stimulation with histamine, an elevation of several [3H]IPs, in particular [3H]1,4-IP2, [3H]1,4,5-IP3 and [3H]1,3,4,5-IP4, above the control values was observed. Following an incubation of 10 or 15 sec with histamine, the content of [3H]1,4,5-IP3 declined towards its basal value, while the amount of metabolites ([3H]4-IP, [3H]1,4-IP2, [3H]1,3,4-IP3) increased with time; [3H]1,3,4,5-IP4 varied little between 5 and 10 sec and decreased at 15 sec. SMC responded also to carbachol and to prostaglandin F2 alpha (PGF2 alpha) by an enhanced production of [3H]IPs, whereas neurokinin A (NKA) had no effect on the turnover of [3H]IPs. Histamine, carbachol and PGF2 alpha evoked a transient elevation in [Ca2+]i, followed by a sustained increase. The duration of the transient elevation appeared similar to that of the increase in [3H]1,4,5-IP3. These results suggest that the 'phospholipase C-1,4,5-IP3-Ca2+ release' signalling pathway is involved in the physiological response of human airway SMC to histamine, carbachol and PGF2 alpha.