Jpn. J. Pharmacol. 71 (2), 161-166 (1996)

Effects of Omega-Conotoxin GVIA on the Activation of Capsaicin-Sensitive Afferent Sensory Nerves in Guinea Pig Airway Tissues

Hiroshi Morimoto, Atsushi Matsuda, Makoto Ohori and Takashi Fujii

Department of Pharmacology, New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, 2-chome, Kashima, Yodogawa-ku, Osaka 532, Japan

Abstract: We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1 - 20 microg/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 microg/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 microg/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 microg/kg) had no effect. However, CgTX (20 microg/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 microg/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01 - 10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

Keywords: N-type Ca2+ channel, Substance P release, Sensory nerve, Airway

Copyright© The Japanese Pharmacological Society 1996

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