Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.
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 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/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.
Morimoto
H
H
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Matsuda
A
A
Ohori
M
M
Fujii
T
T
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000294:innervation; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D013373:Substance P / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D010455:Peptides; D013373:Substance P; D020866:omega-Conotoxin GVIA; D002211:Capsaicin