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

• Published in: Neuroscience research Vol. 53; no. 2; pp. 210 - 215
• Main Authors: Yoshihara, Shigemi, Morimoto, Hiroshi, Ohori, Makoto, Yamada, Yumi, Abe, Toshio, Arisaka, Osamu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.10.2005
• Subjects: Airway; Animals; Bronchi - drug effects; C-fibers; Corticosterone - analogs & derivatives; Corticosterone - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Ganglionic Stimulants - pharmacology; Guinea Pigs; Guinea-pig; K + channels; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Neuroactive steroid; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Organ Culture Techniques; Potassium Channels, Voltage-Gated - drug effects; Quaternary Ammonium Compounds - pharmacology; Substance P; Substance P - metabolism; C-fibers; K + channels; Neuroactive steroid; Guinea-pig; Substance P; Airway
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2005.06.017

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 μg/ml) dose-dependently inhibited electrical field stimulation-induced guinea-pig bronchial smooth muscle contraction, but not the substance P-induced contraction at 1.0 μg/ml. Allotetrahydrocorticosterone (0.01–1.0 μg/ml) also reduced the capsaicin-induced release of substance P-like immunoreactivity 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.