Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats

E. Martínez-García, B. García-Iglesias, J. A. Terrón
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引用次数: 10

Abstract

1 It has been hypothesized that craniovascular 5-HT receptors mediating dilatation of cranial vessels undergo sensitization on decreased serotonergic transmission in migraine. This study analysed the effect of chemical lesion of the 5-HT system in the brain with 5,7-dihydroxytryptamine (5,7-DHT) on 5-HT receptor-mediated dilator responses to 5-carboxamidotryptamine (5-CT) in the middle meningeal artery of anaesthetized rats. 5-CT has recently been shown to elicit dilator responses in this cranial vessel via 5-HT7 receptors and, to a much lesser extent, 5-HT1B/1D receptors.

2 Pretreatment with 5,7-DHT produced a drastic and selective decrease of 5-HT levels in the brain (78 ± 6% and 94 ± 2% in dorsal raphe and hypothalamic paraventricular nuclei, respectively) compared with controls (1% ascorbic acid).

3 Topical application of 5-CT (1–1000 μm) to exposed dura mater encephali produced concentration-dependent decreases in diastolic blood pressure and dilator responses in the middle meningeal artery that were similar in vehicle- and 5,7-DHT-pretreaed animals.

4 Hypotensive and meningeal dilator responses to 5-CT were unaltered by the 5-HT1B/1D receptor antagonist, GR-127935 (1 mg kg−1, i.v.), but were strongly inhibited by the 5-HT7 receptor antagonist, SB-269970 (1 mg kg−1, i.v.), with similar efficacy, in both groups of animals. Treatment with GR-127935 + SB-269970 (1 mg kg−1, i.v. each), produced a stronger inhibitory effect than individual treatments on hypotensive but not on meningeal responses to 5-CT. Meningeal 5-HT7 receptor-mediated responses (i.e. in GR-127935-pretreated animals) were unchanged by 5,7-DHT pretreatment.

5 Results suggest that the sensitivity of craniovascular 5-HT7 receptors mediating dilatation is unaffected by a decrease of 5-HT levels in the brain. A neuronal involvement of 5-HT in migraine seems more likely, therefore.

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中枢5-羟色胺缺失对麻醉大鼠脑膜中动脉5-HT受体介导的血管舒缩反应的影响
1据推测,在偏头痛患者中,介导颅血管扩张的5-羟色胺受体对5-羟色胺能传递减少有增敏作用。本研究分析了5,7-二羟色胺(5,7- dht)化学损伤脑内5- ht系统对麻醉大鼠脑膜中动脉5- ht受体介导的5-羧氨基色胺(5- ct)扩张反应的影响。最近的研究表明,5-CT通过5-HT7受体和5-HT1B/1D受体在颅血管中引起扩张反应,但程度要小得多。2与对照组(1%抗坏血酸)相比,5,7- dht预处理使大脑中5- ht水平急剧和选择性降低(中缝背核和下丘脑室旁核分别为78±6%和94±2%)。在暴露的脑膜上局部应用5- ct (1-1000 μm),会产生浓度依赖性的舒张压降低和脑膜中动脉的扩张反应,这与对照剂和5,7- dht预处理的动物相似。4 . 5-HT1B/1D受体拮抗剂GR-127935 (1 mg kg -1,静脉注射)对5-CT的降压和脑膜扩张反应没有改变,但5-HT7受体拮抗剂SB-269970 (1 mg kg -1,静脉注射)在两组动物中具有相似的疗效。用GR-127935 + SB-269970(各1 mg kg -1,静脉注射)治疗,对降压产生比单独治疗更强的抑制作用,但对脑膜对5-CT的反应没有抑制作用。脑膜5- ht7受体介导的反应(即gr -127935预处理的动物)在5,7- dht预处理后没有变化。结果表明,脑内5- ht水平的降低不影响脑血管5- ht7受体介导扩张的敏感性。因此,偏头痛中5-羟色胺的神经元参与似乎更有可能。
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