Stimulation of dopamine D1 receptors increases activity of periventricular somatostatin neurons and suppresses concentrations of growth hormone
Stimulation of dopamine D1 receptors increases activity of periventricular somatostatin neurons and suppresses concentrations of growth hormone
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DOI：
10.1016/s0739-7240(98)00011-3
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发表时间：
1998-07-01
影响因子：
2.1
通讯作者：
Tucker, HA
中科院分区：
文献类型：
--
作者：
McMahon, CD;Chapin, LT;Tucker, HA
选择性多巴胺D-1受体激动剂SKF 38393刺激灌流牛下丘脑脑片释放生长抑素（SS）。因此，我们假设SKF 38393激活SS神经元，通过释放SS，抑制小牛血清中生长激素（GH）的浓度。我们的目的是确定SKF 38393是否：（1）增加室周核（PeVN）和弓状核（ARC）生长抑素神经元中检测到的免疫反应性c-Fos蛋白和Fos相关抗原（Fos/FRA）的百分比;（2）降低血清中GH的浓度;（3）抑制生长激素释放激素（GHRH）诱导的GH释放。使用膳食喂养的阉牛来执行这些目标，因为GH的同步脉冲发生在每天允许获得饲料的阉牛中喂养前1-2小时。在实验1中，两组四个荷斯坦牛皮下注射。用媒介物（无菌水）或SKF 38393（5 mg/kg BW）。100分钟后，用致死剂量的戊巴比妥钠静脉注射阉牛，并用4%多聚甲醛固定它们的大脑。双标记免疫组织化学进行了40 μ m的自由浮动部分使用抗血清SS和Fos/FRA的部分含有PeVN和ARC核。在PeVN中检测到的SS神经元多于ARC。在PeVN中，SKF 38393处理的SS神经元中存在免疫反应性Fos/FRA的百分比是注射溶剂的阉牛的2.9倍，但在ARC中没有变化。在实验2中，8头荷斯坦牛被皮下注射。在进食前140分钟给予媒介物（无菌水）或SKF 38393（5 mg/kg BW）。与对照组相比，SKF 38393处理的阉牛血清中GH浓度在饲喂前140分钟内没有增加。在实验3中，8头荷斯坦牛被皮下注射。用媒介物（无菌水）或SKF 38393（5 mg/kg BW），然后100分钟后，用[Leu（27），Hse（45）] bGHRH（1-45）内酯（0.2 μ g/kg BW）静脉内注射每只阉牛。牛GHRH。两组均刺激GH释放到血清中，但SKF 38393处理的公牛GH浓度较低。这些结果表明，D-1受体的刺激选择性地增加SS神经元在PeVN的活动，这种增加的活动与抑制基础和GHRH诱导的GH在血清中的膳食喂养的阉牛释放。(C)Elsevier Science Inc. 1998.
The selective dopamine D-1 receptor agonist, SKF38393, stimulates release of somatostatin (SS) from perifused bovine hypothalamic slices. Therefore, we hypothesized that SKF38393 activates SS neurons, which, via release of SS, would suppress concentrations of growth hormone (GH) in serum in calves. Our objectives were to determine whether SKF38393: (1) increases the percent of immunoreactive c-Fos protein and Fos-related antigens (Fos/FRA) detected in somatostatin neurons in periventricular (PeVN) and arcuate (ARC) hypothalamic nuclei; (2) reduces concentrations of GH in serum; (3) suppresses growth hormone-releasing hormone (GHRH)-induced release of GH. Meal-fed steers were used to perform these objectives because a synchronous pulse of GH occurs 1-2 hr before feeding in steers allowed access to feed for 2 hr each day. In Experiment 1, two groups of four Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW). Steers were injected i.v. with a lethal dose of sodium pentobarbital 100 min later and their brains were fixed with 4% paraformaldehyde. Dual-Label immunohistochemistry was performed on 40 mu m free-floating sections using antiserum to SS and to Fos/FRA on sections containing PeVN and ARC nuclei. More SS neurons were detected in the PeVN than in the ARC. The percent of SS neurons with immunoreactive Fos/FRA present was 2.9-fold higher in SKF38393-treated compared with vehicle-injected steers in the PeVN, but was unchanged in the ARC. In Experiment 2, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW) 140 min before meal-feeding. In contrast to controls, concentrations of GH in serum of SKF38393-treated steers did not increase during the 140 min before meal-feeding. In Experiment 3, eight Holstein steers were injected s.c. with either vehicle (sterile water) or SKF38393 (5 mg/kg BW), then 100 min later, each steer was injected i.v. with [Leu(27), Hse(45)] bGHRH(1-45) lactone (0.2 mu g/kg BW). Bovine GHRH. stimulated release of GH into serum in both groups, but concentrations of GH were lower in SKF38393-treated steers. These results show that stimulation of D-1 receptors selectively increases activity of SS neurons in the PeVN, and this increased activity is associated with suppressed basal- and GHRH-induced release of GH in serum of meal-fed steers. (C) Elsevier Science Inc. 1998.