Chapin E M, Andrade R
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Pharmacol Exp Ther. 2001 Apr;297(1):395-402.
Little is currently known regarding the electrophysiological response elicited by 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation in the brain. Previous anatomical studies have shown that the anterior thalamus expresses a high density of 5-HT7 receptors. Therefore, we used whole-cell recording techniques in the in vitro brain slices to examine the effects of serotonin on neurons of the anterodorsal nucleus of the thalamus (ADn). Bath application of 5-HT induces a large membrane depolarization and inward current in neurons of the ADn. Since these cells expressed 5-HT7 receptor mRNA, as determined by single-cell reverse transcriptase-polymerase chain reaction, we pharmacologically characterized the 5-HT receptor mediating this response. We found that the 5-HT1 and 5-HT7 agonists 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine mimicked the response to 5-HT, whereas the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine did not. Consistent with the involvement of a 5-HT7 receptor, 5-CT was approximately 18 times more potent than 5-HT. Furthermore, administration of the 5-HT(1A) and 5-HT7 agonist 8-hydroxydipropylaminotetralin mimicked and antagonized the effect of serotonin, suggesting it acted as a partial agonist. To determine if either the 5-HT1 or 5-HT7 receptor mediated the 5-HT-induced inward current, we used antagonists. We found that the 5-HT7 ligands ritanserin, methylsergide, LSD, and mesulergine could inhibit the 5-HT-induced inward current, whereas the 5-HT1 antagonist cyanopindolol had no effect. The pA(2) value determined for mesulergine closely approximated that expected for a 5-HT7 receptor. Finally, we found that bath application of the selective antagonist SB-269770 blocks the 5-HT-induced inward current. These results identify the receptor mediating the serotonin-induced membrane depolarization in the ADn as the 5-HT7 subtype.
目前对于5-羟色胺-7（5-HT(7)）受体刺激在大脑中引发的电生理反应知之甚少。先前的解剖学研究表明，前丘脑表达高密度的5-HT7受体。因此，我们在体外脑片中使用全细胞记录技术来研究血清素对丘脑前背核（ADn）神经元的影响。在ADn神经元中，浴加5-HT可诱导大的膜去极化和内向电流。通过单细胞逆转录聚合酶链反应确定，由于这些细胞表达5-HT7受体mRNA，我们从药理学角度对介导该反应的5-HT受体进行了表征。我们发现5-HT1和5-HT7激动剂5-羧酰胺色胺（5-CT）和5-甲氧基色胺可模拟对5-HT的反应，而5-HT2激动剂2,5-二甲氧基-4-碘苯丙胺则不能。与5-HT7受体的参与一致，5-CT的效力比5-HT高约18倍。此外，给予5-HT(1A)和5-HT7激动剂8-羟基二丙基氨基四氢萘可模拟并拮抗血清素的作用，表明它作为部分激动剂起作用。为了确定是5-HT1还是5-HT7受体介导了5-HT诱导的内向电流，我们使用了拮抗剂。我们发现5-HT7配体利坦色林、甲基麦角新碱、麦角酸二乙胺和美舒麦角可以抑制5-HT诱导的内向电流，而5-HT1拮抗剂氰吲哚洛尔则没有作用。美舒麦角的pA(2)值与5-HT7受体预期的值非常接近。最后，我们发现浴加选择性拮抗剂SB-269770可阻断5-HT诱导的内向电流。这些结果表明，介导ADn中血清素诱导的膜去极化的受体是5-HT7亚型。
