Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats.
Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats.
复制标题
中枢血清素耗竭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。
DOI：
10.1111/j.1474-8673.2009.00430.x
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Terrón,JA
中科院分区：
文献类型：
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作者：
Martínez-García,E;García-Iglesias,B;Terrón,JA
1据推测，介导颅血管扩张的颅血管5-HT受体在偏头痛中对降低的多巴胺能传递敏感。本研究分析了用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-羧酰胺色胺（5-CT）扩张反应的影响。最近显示5-CT通过5-HT 7受体和5-HT 1B/1D受体在该颅血管中引起扩张反应，但程度要小得多。2用5，7-DHT预处理可使脑中5-HT水平急剧和选择性降低（中缝 背核和下丘脑室旁核中分别为78 ± 6%和94 ± 2%，3局部应用5-CT（1-1000 μm）暴露的硬脑膜引起脑膜中动脉舒张压和扩张反应的浓度依赖性降低，溶剂和5，7-DHT预处理动物。4 5-CT的低血压和脑膜扩张反应未被5-HT 1B/1D受体拮抗剂GR-127935（1 mg kg−1，i. v.）改变，但被5-HT 7受体拮抗剂SB-269970（1 mg kg−1，i. v.）强烈抑制， 在两组动物中具有相似的功效。GR-127935 + SB-269970（各1 mg kg−1，i. v.）给药对水肿的抑制作用强于单独给药，但对5-CT的脑膜反应无抑制作用。 脑膜5-HT 7受体介导的反应（即GR-127935预处理动物）未受5，7-DHT预处理的影响。5结果表明，脑血管5-HT 7受体介导扩张的敏感性不受脑中5-HT水平降低的影响。因此，偏头痛中5-HT的神经元参与似乎更有可能。
1It 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‐HT7receptors and, to a much lesser extent, 5‐HT1B/1Dreceptors.2Pretreatment 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).3Topical 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.4Hypotensive and meningeal dilator responses to 5‐CT were unaltered by the 5‐HT1B/1Dreceptor antagonist, GR‐127935 (1 mg kg−1, i.v.), but were strongly inhibited by the 5‐HT7receptor 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‐HT7receptor‐mediated responses (i.e. in GR‐127935‐pretreated animals) were unchanged by 5,7‐DHT pretreatment.5Results suggest that the sensitivity of craniovascular 5‐HT7receptors 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.