Uvnäs-Moberg K, Ahlenius S, Alster P, Hillegaart V
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Neuroendocrinology. 1996 Mar;63(3):269-74. doi: 10.1159/000126970.
Male Sprague-Dawley rats were given one of the 5-HT receptor agonists 8-OH-DPAT (0.5-2.0 mg kg-1), TFMPP (0.125-2.0 mg kg-1), DOI (0.125-2.0 mg kg-1), and m-CPBG (1.25-20.0 mg kg-1), selective for 5-HT1A, 5-HT1B, 5-HT2 and the 5-HT3 receptors, respectively, or one of the DA receptor agonists bromocriptine (2.0-32.0 mg kg-1), quinpirole (0.5-8.0 mg kg-1) and 7-OH-DPAT (0.2-3.2 mg kg-1), selective for DA D2, DA D2/D3 and DA D3 receptors, respectively. An additional group of animals was given buspirone (2.0-8.0 mg kg-1) a 5-HT1A receptor agonist and DA D2 receptor antagonist. Separate groups of rats were given both the 5-HT1A receptor antagonist pindolol and 8-OH-DPAT or both the DA D2/D3 receptor antagonist raclopride and 7-OH-DPAT. Blood samples were collected 30 min (in some cases 120 min) after drug administration and assayed for insulin, glucagon and glucose levels. The 5-HT1A receptor agonist 8-OH-DPAT produced a statistically significant decrease in plasma insulin levels and an increase in glucose, whereas glucagon levels were unaffected. The only effect observed after buspirone treatment was a small increase in plasma glucose levels. No significant effects on plasma insulin, glucagon or glucose were seen after treatment with the 5-HT1B, 5-HT2 or 5-HT3 agonists. The DA D3 receptor agonist 7-OH-DPAT produced a decrease in plasma insulin (3.2 mg kg-1, 120 min) and an increase in glucose levels. Administration of the DA D2/D3 receptor agonist quinpirole resulted only in increased plasma glucose, whereas the DA D2 receptor agonist bromocriptine had no effect. In support of a separate mediation of glucose secretion by 5-HT1A and DA D3 receptors, the effects of 8-OH-DPAT on glucose levels were antagonized by (-)pindolol pretreatment, and the 7-OH-DPAT-induced effects on glucose levels were antagonized by raclopride pretreatment. It is concluded that plasma glucose levels are under separate serotonergic and dopaminergic control, exerted via 5-HT1A and DA D3 receptors, respectively.
将雄性斯普拉格 - 道利大鼠分别给予5种5 - 羟色胺（5 - HT）受体激动剂之一：8 - 羟基 - 二丙基氨基四氢吡啶（8 - OH - DPAT，0.5 - 2.0毫克/千克）、三氟甲基苯基哌嗪（TFMPP，0.125 - 2.0毫克/千克）、1,2 - 二甲基吲哚（DOI，0.125 - 2.0毫克/千克）和间氯苯基胍（m - CPBG，1.25 - 20.0毫克/千克），它们分别对5 - HT1A、5 - HT1B、5 - HT2和5 - HT3受体具有选择性；或者给予3种多巴胺（DA）受体激动剂之一：溴隐亭（2.0 - 32.0毫克/千克）、喹吡罗（0.5 - 8.0毫克/千克）和7 - 羟基 - 二丙基氨基四氢吡啶（7 - OH - DPAT，0.2 - 3.2毫克/千克），它们分别对DA D2、DA D2/D3和DA D3受体具有选择性。另外一组动物给予丁螺环酮（2.0 - 8.0毫克/千克），它是一种5 - HT1A受体激动剂和DA D2受体拮抗剂。将大鼠分成不同组，分别给予5 - HT1A受体拮抗剂吲哚洛尔和8 - OH - DPAT，或者给予DA D2/D3受体拮抗剂雷氯必利和7 - OH - DPAT。给药30分钟（某些情况下为120分钟）后采集血样，检测胰岛素、胰高血糖素和葡萄糖水平。5 - HT1A受体激动剂8 - OH - DPAT使血浆胰岛素水平出现具有统计学意义的下降，葡萄糖水平升高，而胰高血糖素水平未受影响。丁螺环酮治疗后唯一观察到的效应是血浆葡萄糖水平略有升高。用5 - HT1B、5 - HT2或5 - HT3激动剂治疗后，对血浆胰岛素、胰高血糖素或葡萄糖均未观察到显著影响。DA D3受体激动剂7 - OH - DPAT使血浆胰岛素水平下降（3.2毫克/千克，120分钟），葡萄糖水平升高。给予DA D2/D3受体激动剂喹吡罗仅导致血浆葡萄糖水平升高，而DA D2受体激动剂溴隐亭则无作用。为支持5 - HT1A和DA D3受体对葡萄糖分泌的独立调节作用，（ - ）吲哚洛尔预处理可拮抗8 - OH - DPAT对葡萄糖水平的影响，雷氯必利预处理可拮抗7 - OH - DPAT对葡萄糖水平的影响。由此得出结论，血浆葡萄糖水平分别受5 - HT能和多巴胺能的独立控制，分别通过5 - HT1A和DA D3受体发挥作用。
