Aono Y, Saigusa T, Watanabe S, Iwakami T, Mizoguchi N, Ikeda H, Ishige K, Tomiyama K, Oi Y, Ueda K, Rausch W-D, Waddington J L, Ito Y, Koshikawa N, Cools A R
Department of Pharmacology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
J Neural Transm (Vienna). 2007 Sep;114(9):1135-42. doi: 10.1007/s00702-007-0745-1. Epub 2007 May 29.
Microdialysis technique was used to study the effects of the locally applied alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine-elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving rats. Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32% and phentolamine blocked this effect. Phentolamine elevated the basal noradrenaline efflux by 150% and phenylephrine counteracted this effect. The desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine and potentiated those of phentolamine. These results indicate that the accumbal noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are suggested to be presynaptically located on adrenergic nerve terminals in the NAc. Furthermore, this study suggests that the conformational state of alpha adrenoceptors varies across the available amount of noradrenaline. The clinical impact of these data is discussed.
采用微透析技术研究了局部应用α-肾上腺素能受体激动剂去氧肾上腺素和拮抗剂酚妥拉明对自由活动大鼠伏隔核（NAc）基础去甲肾上腺素外流以及去甲肾上腺素摄取抑制剂地昔帕明引起的去甲肾上腺素外流的影响。河豚毒素使基础去甲肾上腺素外流减少72%，而去甲肾上腺素再摄取抑制剂地昔帕明使基础去甲肾上腺素外流增加204%。去氧肾上腺素使基础去甲肾上腺素外流减少32%，酚妥拉明可阻断此效应。酚妥拉明使基础去甲肾上腺素外流增加150%，而去氧肾上腺素可抵消此效应。地昔帕明引起的去甲肾上腺素外流不受去氧肾上腺素影响，但可被酚妥拉明增强。地昔帕明可抵消去氧肾上腺素的作用并增强酚妥拉明的作用。这些结果表明，伏隔核去甲肾上腺素外流受α-肾上腺素能受体的抑制性控制，提示这些受体位于NAc肾上腺素能神经末梢的突触前。此外，本研究表明，α-肾上腺素能受体的构象状态随去甲肾上腺素的可用量而变化。讨论了这些数据的临床意义。
