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通过抑制蛋白激酶来阻断神经降压素诱导的运动活性。

Blockade of neurotensin-induced motor activity by inhibition of protein kinase.

作者信息

Kalivas P W

机构信息

Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman.

出版信息

Psychopharmacology (Berl). 1994 Feb;114(1):175-80. doi: 10.1007/BF02245461.

DOI:10.1007/BF02245461
PMID:7846201
Abstract

The administration of neurotensin into the ventral tegmental area stimulates dopamine neurons and locomotor activity. Furthermore, when neurotensin is microinjected daily into the ventral tegmental area the motor stimulant response increases. The role of protein kinases in the motor stimulant effect of neurotensin was evaluated by coadministration of the protein kinase inhibitors H8 and H7 into the ventral tegmental area with neurotensin. It was found that the acute motor stimulant effect of neurotensin was abolished in a dose-dependent fashion by H8 coadministration. Neurotensin-induced activity was also blocked by H7. However, acute motor stimulation following microinjection of the mu opioid, Tyr-d-Ala-Gly-MePhe-Gly(ol) or the potassium channel antagonist apamin into the ventral tegmental area was not affected by coadministration with H8. The behavioral sensitization produced by daily neurotensin microinjection into the ventral tegmental area was also prevented by the coadministration of H8. These data indicate that the motor stimulation produced by acute and repeated neurotensin microinjection into the ventral tegmental area is dependent upon activation of protein kinase(s). Furthermore, Tyr-d-Ala-Gly-MePhe-Gly(ol) and apamine elicit locomotion independently of protein kinase(s).

摘要

向腹侧被盖区注射神经降压素会刺激多巴胺神经元和运动活性。此外,当每天向腹侧被盖区微量注射神经降压素时,运动刺激反应会增强。通过将蛋白激酶抑制剂H8和H7与神经降压素共同注射到腹侧被盖区,评估了蛋白激酶在神经降压素运动刺激作用中的作用。发现与H8共同注射时,神经降压素的急性运动刺激作用以剂量依赖的方式被消除。神经降压素诱导的活性也被H7阻断。然而,向腹侧被盖区微量注射μ阿片样物质、酪氨酰 - d - 丙氨酰 - 甘氨酰 - 甲硫苯丙氨酰 - 甘氨醇(Tyr - d - Ala - Gly - MePhe - Gly(ol))或钾通道拮抗剂蜂毒明肽后产生的急性运动刺激不受与H8共同注射的影响。每天向腹侧被盖区微量注射神经降压素所产生的行为敏化也被与H8共同注射所阻止。这些数据表明,向腹侧被盖区急性和重复微量注射神经降压素所产生的运动刺激依赖于蛋白激酶的激活。此外,酪氨酰 - d - 丙氨酰 - 甘氨酰 - 甲硫苯丙氨酰 - 甘氨醇(Tyr - d - Ala - Gly - MePhe - Gly(ol))和蜂毒明肽引发运动独立于蛋白激酶。

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Studies on neurotensin catecholamine interactions in the hypothalamus and in the forebrain of the male rat.雄性大鼠下丘脑和前脑内神经降压素与儿茶酚胺相互作用的研究。
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