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5-羟色胺对大鼠脑中生长抑素受体-效应器系统及生长抑素水平的调节作用

Modulation by 5-hydroxytryptamine of the somatostatin receptor-effector system and somatostatin levels in rat brain.

作者信息

Muñoz-Acedo G, Arilla E

机构信息

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.

出版信息

Brain Res Mol Brain Res. 1996 Apr;37(1-2):259-66. doi: 10.1016/0169-328x(95)00326-n.

DOI:10.1016/0169-328x(95)00326-n
PMID:8738159
Abstract

The role of 5-hydroxytryptamine (5-HT) in the acute regulation of the rat brain somatostatin (SS) receptor-effector system and somatostatin-like immunoreactivity (SSLI) content was examined. 5-HT administered i.c.v. in a volume of 10 microliters at a dose of 0.5 microgram (pH 3.4) increased the SSLI concentration at 60 min in the Wistar rat frontoparietal cortex and hippocampus (60%, P < 0.05; 72%, P < 0.01; respectively). These changes were associated with a significant increase in the total number of specific SS receptors in the frontoparietal cortex (24%, P < 0.05) and hippocampus (20%, P < 0.05), without changes in the affinity constant as compared with the control group. No significant differences were seen in the basal and forskolin (FK)-stimulated adenylate cyclase (AC) activities in both brain areas of 5-HT-treated rats when compared to the control group. The capacity of SS to inhibit the FK-stimulated AC activity in the frontoparietal cortex and hippocampus of 5-HT-treated rats was lower than in the control groups. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in frontoparietal cortical and hippocampal membranes was markedly decreased in 5-HT-treated rats. To determine if the above-mentioned changes were related to the 5-HT activation of central 5-HT1 and 5-HT2 receptors, a non-selective 5-HT1 and 5-HT2 receptor antagonist, methysergide, was administered 60 min before the 5-HT injection. Pretreatment with methysergide (5 mg/kg i.p. in a volume of 400 microliters) prevented the 5-HT-induced changes in the SS receptor-effector system and in SSLI levels in both brain areas. Methysergide alone had no observable effect on the somatostatinergic system. These results suggest that the frontoparietal cortical and hippocampal somatostatinergic system can be regulated by 5-HT receptors.

摘要

研究了5-羟色胺(5-HT)在大鼠脑生长抑素(SS)受体效应系统和生长抑素样免疫反应性(SSLI)含量急性调节中的作用。以0.5微克(pH 3.4)的剂量、10微升的体积经脑室内注射5-HT,可使Wistar大鼠额顶叶皮质和海马中的SSLI浓度在60分钟时增加(分别为60%,P<0.05;72%,P<0.01)。这些变化与额顶叶皮质(24%,P<0.05)和海马(20%,P<0.05)中特异性SS受体总数的显著增加相关,与对照组相比,亲和常数无变化。与对照组相比,5-HT处理大鼠的两个脑区中基础和福司可林(FK)刺激的腺苷酸环化酶(AC)活性均无显著差异。5-HT处理大鼠的额顶叶皮质和海马中,SS抑制FK刺激的AC活性的能力低于对照组。在5-HT处理的大鼠中,稳定的GTP类似物5'-鸟苷酰亚胺二磷酸(Gpp(NH)p)抑制额顶叶皮质和海马膜中FK刺激的AC活性的能力明显降低。为了确定上述变化是否与5-HT对中枢5-HT1和5-HT2受体的激活有关,在注射5-HT前60分钟给予非选择性5-HT1和5-HT2受体拮抗剂美西麦角。用美西麦角(5毫克/千克腹腔注射,体积为400微升)预处理可防止5-HT诱导的两个脑区中SS受体效应系统和SSLI水平的变化。单独使用美西麦角对生长抑素能系统无明显影响。这些结果表明,额顶叶皮质和海马的生长抑素能系统可受5-HT受体调节。

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