| Summary: | 碩士 === 高雄醫學院 === 醫學研究所 === 87 === The effects of glyceryl nonivamide (GLNVA) and sodium nonivamide acetate (SNA) on isolated tracheal smooth muscle of guinea-pig in vitro and the desensitizing effect of GLNVA and SNA in anesthetized guinea-pig airways in vivo were first investigated. Both GLNVA (0.01-10 uM) and SNA (0.01-100 uM) produced concentration-dependent contraction in the isolated guinea-pig trachea, and this effect were inhibited by pretreatment with capsazepine (10 uM), ruthenium red (10 uM), theophylline (10 uM), or sensory denervation, respectively. On the other hand, at higher concentration, GLNVA 5 uM could produce relaxation on carbachol-induced contracted tracheal smooth muscle after sensory denervation. Moreover, this relaxation effect was completely blocked by indomethacin (10 uM) and partially blocked by TEA (tetraethylammonium, non-selective potassium channel blocker, 10-2 M), glibenclamide (10 uM), theophylline (10 uM), 8-PT (8-phenyltheophylline, adenosine A1 receptor antagonist, 10 uM) and DMPX (3,7-dimethyl-1-propargylxanthine, adenosine A2 receptor antagonist, 10 uM) . After long-term pretreatment of GLNVA and SNA (105.6 mg, 7 days, s.c.), GLNVA significantly inhibited ovalbumin- or capsaicin-induced tracheal smooth muscle contraction, but SNA did not. In anesthetized guinea-pig, long term treatment of GLNVA and SNA, also significantly inhibited capsaicin-induced pulmonary dysfunction. The distribution of SP-like immunoreactive nerves in guinea pig airway was also displayed in this study. In the present study we find that capsaicin and the nonpungent capsaicin analogue GLNVA can deplete the SP from sensory nerve in guinea pig trachea. In conclusion, the present data indicated that, capsaicin, GLNVA and SNA caused chemical desensitization of sensory nerve in guinea-pig tracheal smooth muscle and renders them insensitive to further exposure of capsaicin. The tracheal hyperresponsivess of guinea-pig induced by ovalbumin were attenuated following chronic treatment with capsaicin, GLNVA and SNA which destroys sensory C-fiber. GLNVA induced- relaxation effect was mediated via the activation of ATP-sensitive K+ channel opening, adenosine receptor modulation and release of endogenous prostanoids of the smooth muscle.
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