A neuroactive steroid, allotetrahydrocorticosterone inhibits sensory nerves activation in guinea-pig airways

We examined the effects of a neuroactive steroid, allotetrahydrocorticosterone on the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). Allotetrahydrocorticosterone (0.0001-1.0 mu g/ml) dose-dependently inhibited electrical field stimulation-induced guinea-pig bronchial smooth muscle contraction, but not the substance P-induced contraction at 1.0 mu g/ml. Allotetrahydrocorticosterone (0.01-1.0 mu g/ml) also reduced the capsaicin-induced release of substance P-like immumoreactivity from guinea-pig airway tissues in a dose-dependent manner. The inhibitory effect of allotetrahydrocorticosterone on electrical field stimulation-induced bronchial contraction were reduced by the pretreatment of voltage-dependent K+ channel blockers, tetraethylammonium (1 mM). This evidence suggests that allotetrahydrocorticosterone negatively modulate the activation of C-fibers and substance P release from their endings in airway tissues via the opening of voltage-dependent K+ channels. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.