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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats.
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Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats.

机译：RS14203对麻醉大鼠中5-羟色胺能途径的选择性增强作用。

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摘要

The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the treatment of inflammation and pulmonary diseases is limited by their side effects: nausea and vomiting. We studied the effect of three structurally diverse PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered at 1, 10, or 100 microg/kg (iv) 15 min prior to the induction of bradycardia by an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal electrical stimulation. At 100 microg/kg, RS14203 significantly potentiated the 2-methyl-5-HT response. No statistically significant effects were observed with (R)-rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1-100 microg/kg iv) did not affect the bradycardia induced by vagal electrical stimulation. Consequently, our results show that RS14203 selectively facilitates serotoninergic neurotransmission in vagal afferent fibers. The emetic action of RS14203 may be mediated by this mechanism.
机译：选择性4型磷酸二酯酶（PDE4）抑制剂在治疗炎症和肺部疾病方面的有效性受到其副作用的限制：恶心和呕吐。我们研究了三种结构不同的PDE4抑制剂对麻醉大鼠迷走神经传入和传出纤维的影响。在von Bezold-Jarisch反射（迷走神经传入纤维）和迷走神经电刺激模型（迷走神经传入纤维）中评估了RS14203，（R）-咯利普兰和CT-2450的作用。在静脉注射2-甲基-5-HT（von Bezold-Jarisch reflex）或迷走性电刺激诱发心动过缓之前，所有三种PDE4抑制剂的给药时间分别为1、10或100 microg / kg（iv）15分钟。刺激。在100微克/千克下，RS14203显着增强了2-甲基-5-HT反应。 （R）-咯利普兰或CT-2450在所研究的剂量下未观察到统计学上显着的影响。 RS14203，（R）-咯利普兰或CT-2450（1-100微克/千克，静脉注射）不影响迷走神经电刺激引起的心动过缓。因此，我们的结果表明，RS14203选择性促进迷走神经传入纤维中的5-羟色胺能神经传递。 RS14203的催吐作用可能通过这种机制介导。

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