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多年英语培训经验，教授科目全面、多样。尤其擅长基础出国英语，实用口语教学，各类实用写作。对各个科目都有自己的独特见解和教学方式。课堂气氛融洽轻松深受学生喜爱。相信教师是一个伟大的职业，可以改变并影响着很多人。

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    188宝金博页面版: Lipoxin A(sub)4( sub) inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea

    下载积分： 1992

    内容提示： ELSEVIER European Journal of Pharmacology 287 (1995) 233-238 ejp Lipoxin A 4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea Jun Tamaoki *, Etsuko Tagaya, Isao Yamawaki, Kimio Konno First Department of Medicine, Tokyo Women's Medical College, Tokyo 162, Japan Received 30 March 1995; revised 1 August 1995; accepted 4 August 1995 Abstract The effect of lipoxin A 4 and lipoxin B 4 on cholinergic neurotransmission in rabbit tracheal segments was studied under isomet...

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    ELSEVIER European Journal of Pharmacology 287 (1995) 233-238 ejp Lipoxin A 4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea Jun Tamaoki *, Etsuko Tagaya, Isao Yamawaki, Kimio Konno First Department of Medicine, Tokyo Women's Medical College, Tokyo 162, Japan Received 30 March 1995; revised 1 August 1995; accepted 4 August 1995 Abstract The effect of lipoxin A 4 and lipoxin B 4 on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. Lipoxin A 4 attenuated the contractile responses to electrical field stimulation and caused a rightward shift of the frequency-response curves, so that the stimulus frequency required to produce a half-maximal effect (ESs0) increased from 8.1 _+ 0.8 to 25.7 _+ 1.9 Hz (P < 0.001), whereas lipoxin B 4 had no effect. In contrast, lipoxin A 4 did not alter the contractile responses to acetylcholine. Pretreatment of tissues with N%nitro-L-arginine methylester inhibited the effect of lipoxin A 4 on electrical field stimulation, but N%nitro-D-arginine methylester did not. This inhibition by N°-nitro-L-arginine methylester was reversed by L-arginine but not by I>arginine. These results suggest that lipoxin A 4 prejunctionally reduces the vagal nerve-mediated contraction of airway smooth muscle, probably by inhibiting the release of acetylcholine, and that this effect may be exerted through stimulation of nitric oxide generation. Keywords: Lipoxin A4; Cholinergic neurotransmission; Nitric oxide (NO); Smooth muscle, airway I. Introduction Lipoxins are a class of biologically active trihydroxy lipids with a conjugated tetraene and are formed by interactions between the 5- and 15-1ipoxygenases within the arachidonic acid cascade (Serhan et al., 1984). The two major compounds, lipoxin A n and lipoxin B4, is 5 S,6 R, 15 S-trihydroxy- 7,9,13 -trans- 11-cis-eicosatetraen- oic acid and 5S,14R,15S-trihydroxy-6,10,12-trans-8-cis- eicosatetraenoic acid, respectively (Serhan et al., 1986a,b). Lipoxin A 4 is ge.nerated by neutrophils, alve- olar macrophages, eosinophils and, possibly, epithelial cells (Sigal and Nadel, 1988), and significant amounts of lipoxin A 4 can be detected in bronchoalveolar lavage fluid obtained from patients with inflammatory pul- monary diseases (Lee eta[., 1990). In addition, lipoxins display biological actions in the airways. For example, lipoxin A 4 contracts lung parenchymal strips but not * Corresponding author. First Department of Medicine, Tokyo Women's Medical College, 8-1 Kawada-Cho, Shinjuku, Tokyo 162, Japan. Tel.: 81-3-3353-8111; fax: 81-3-5379-5457. 0014-2999/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0014-2999(95)00490-z. tracheal smooth muscle preparations in guinea pigs (Dahl6n et al., 1987; Jacques et al., 1988), stimulates airway sensory C-fibers (Manzini and Meini, 1991), and enhances or inhibits neutrophil migration (Palmblad et al., 1987; Lee et al., 1989), whereas lipoxin B 4 does not produce such effects. However, the effect of lipoxins on airway cholinergic neurotransmission is unknown. There is increasing evidence that nitric oxide (NO) may regulate airway smooth muscle and vascular smooth muscle tone, pulmonary neurotransmission and host defence (Gaston et al., 1994). Although an inter- action between lipoxin A 4 and the NO-generating sys- tem remains uncertain, DahI6n et al. (1987) showed that lipoxin A 4 induced arteriolar dilatation in the hamster cheek pouch by stimulating the release of endothelium-derived relaxing factor, which was conse- quently identified as NO. Therefore, in the present study, to determine whether lipoxins alter cholinergic neurotransmission in the airways and, if so, to assess a possible contribution of NO generation, we studied rabbit tracheal ring segments under isometric condi- tions in vitro.

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