下行性の筋緊張制御における脊髄のセロトニン1Aおよび2受容体の役割

脊髓血清素 1A 和 2 受体在下降肌张力控制中的作用

• 批准号: 09672258
• 负责人: ONO Hideki
• 金额: $ 2.3万
• 依托单位: Science University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672258/
• 关键词: serotonin receptor; muscle tone; spinal cord; serotonin release; サイクロベンザプリン

Descending serotonergic neurons originated from the Raphe nuclei innervate spinal motoneurons, and control muscle tone and locomotion. However, the subtypes of the serotonergic receptors and the detailed mechanisms of action are still unclear. In the present study, we studied the followings using the measurement of spinal reflex potentials and serotonin release from the spinal cord in adult rats.1.8-OH-DPAT is widely used as an agonist for 5-HT1A receptor. In this study, we showed that the R- and S-isomers facilitate the spinal motor activity via different types of receptors. At the spinal cord level, the R-isomer depressed the monosynaptic reflex via receptors other than 5-HT1A.2.We showed that cyclobenzaprine, and amitriptyline and cyproheptadine, analogs of cyclobenzaprine blocked the 5-HT2 receptors in the spinal cord, and consequently depressed the monosynaptic reflexes. Involvement of 5-HT2 receptors in motor stimulatory role of serotonergic systems was elucidated.3.Serotonin released from the terminals of descending serotonergic neurons was measured using spinal subarachnoid space perfusion methods. Amitriptyline which blocks 5-HT2 receptors in the spinal cord did not increase serotonin. From this result, uptake inhibitory action of amitriptyline to serotonin was considered to be weaker than 5-HT2 receptor blocking action. Diazepam, which has muscle relaxant action, reduced the release of serotonin.These results suggest that spinal motor systems are facilitated by descending serotonergic systems, especially via 5-HT2 receptors. On the other hand, it was suggested that 5-HT receptors other than 5-HT1A inhibited spinal motor systems.

起源于中缝核的下行多巴胺能神经元支配脊髓运动神经元，并控制肌张力和运动。然而，肾上腺素能受体的亚型和详细的作用机制仍不清楚。在本研究中，我们研究了以下使用测量脊髓反射电位和5-羟色胺从脊髓释放。1.8-OH-DPAT被广泛用作5-HT 1A受体激动剂。在这项研究中，我们发现，R-和S-异构体通过不同类型的受体促进脊髓运动活动。在脊髓水平，R-异构体通过5-HT 1A以外的受体抑制单突触反射。2.我们发现环苯扎林，阿米替林和赛庚啶，环苯扎林的类似物，阻断脊髓中的5-HT 2受体，从而抑制单突触反射。5-HT_2受体参与了多巴胺能神经系统的运动刺激作用。3.用脊髓蛛网膜下腔灌流法测定5-HT_2受体在多巴胺能神经元终末的释放量。阻断脊髓中5-HT 2受体的阿米替林不会增加血清素。根据该结果，认为阿米替林对5-羟色胺的摄取抑制作用弱于5-HT 2受体阻断作用。具有肌肉松弛作用的地西泮可减少5-羟色胺的释放，这些结果表明，脊髓运动系统是由下行的多巴胺能系统，特别是通过5-HT 2受体促进的。另一方面，有人建议，5-HT受体以外的5-HT 1A抑制脊髓运动系统。

项目成果

M. Honda and H. Ono: "Differential effects. of (R)-and (S)-8-hyaroxy-2-(di-n-propylaminc)tetrdlin on the monosynaptic spinal reflex in rats"Eur. J. Pharmacol.. 373. 171-179 (1999)

M. Honda 和 H. Ono：“(R)-和 (S)-8-hyaroxy-2-(二正丙胺)tetrdlin 对大鼠单突触脊髓反射的不同影响”Eur。

M.Honda and H.Ono: "Differential effects of (R)-and (S)-8-hydroxy-2-(di-n-propylamino)tetralin on the monosynaptic spinal reflex in rats."Eur.J.Pharmacol.. 373. 171-179 (1999)

M.Honda 和 H.Ono：“(R)-和 (S)-8-羟基-2-(二正丙氨基)四氢萘对大鼠单突触脊髓反射的不同影响。”Eur.J.Pharmacol。

M.handa and H.Ono: "Differential effects of (R)-and(S)-8-hydroxy-2-(di-n-propylamino)tetralin on the monosynaptic spinal reflex in rats."Eur.J.Pharmacol.. 373. 171-179 (1999)

M.handa 和 H.Ono：“(R)-和(S)-8-羟基-2-(二正丙氨基)四氢萘对大鼠单突触脊髓反射的不同影响。”Eur.J.Pharmacol。