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 microg/ml) dose-dependently inhibited electrical field stimulation-induced guinea-pig bronchial smooth muscle contraction, but not the substance P-induced contraction at 1.0 microg/ml. Allotetrahydrocorticosterone (0.01-1.0 microg/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.
Yoshihara
Shigemi
S
Department of Pediatrics, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.
Morimoto
Hiroshi
H
Ohori
Makoto
M
Yamada
Yumi
Y
Abe
Toshio
T
Arisaka
Osamu
O
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism
D005731:Ganglionic Stimulants; D024642:Potassium Channels, Voltage-Gated; D000644:Quaternary Ammonium Compounds; D013373:Substance P; C003676:tetrahydrocorticosterone; C027917:tetramethylammonium; D003345:Corticosterone