Piwko C, Thoss V S, Samanin R, Hoyer D, Vezzani A
Preclinical Research, SANDOZ Pharma Ltd., Basel, Switzerland.
Neuroscience. 1996 Dec;75(3):857-68. doi: 10.1016/0306-4522(96)00304-1.
In situ hybridization histochemistry with somatostatin sst1-sst5 receptor messenger RNA-selective oligoprobes and quantitative receptor autoradiographic binding studies using [125I]Tyr3-octreotide, [Leu2,D-Trp22,125I-Tyr25]somatostatin-28 and [125I]CGP 23996 ([125I]c[Asn-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) were performed to determine the level of expression of somatostatin receptor messenger RNA and receptor binding sites in the hippocampal formation, limbic system and cerebral cortex of adult rats electrically kindled in the dorsal hippocampus. In control rats (implanted with electrodes but not electrically stimulated), the somatostatin-1 receptor-selective [125I]Tyr3-octreotide and the non-subtype-selective [Leu3,D-Trp22,125I-Tyr25]somatostatin-28 preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the molecular layer of the dentate gyrus, the subiculum and presubiculum of the hippocampal formation, the inner layer of the frontal cortex, and the lateral and basolateral nuclei of the amygdala. The non-subtype-selective radioligand [125I]CGP 23996 (in 5 mM Mg2+ buffer) preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the subiculum and the basolateral nucleus of the amygdala. Under conditions where primarily somatostatin-2 receptors were labelled, [125I]CGP 23996 (in 120 mM Na+ buffer) showed strong binding in the strata oriens and radiatum of the CA1 subfield of the hippocampus and the frontal cortex, whereas the dentate gyrus, subiculum and amygdala showed only weak signals. During and after kindling, no significant differences were observed between the ipsi- and contralateral sides of the hippocampus. A significant decrease (about 40%) of somatostatin receptor binding sites was observed in the molecular layer of the dentate gyrus with all radioligands (except [125I]CGP 23996 in Na+ buffer, which did not label this area) at stage 2 (pre-convulsive stage) and one week, but not one month, after stage 5 (generalized motor seizures). In contrast to somatostatin receptor binding, no alterations of the messenger RNA levels for sst1-sst5 receptors were found either at stage 2 or at stage 5. Similarly, no changes in receptor binding or messenger RNA levels were observed in the brain of rats which experienced a single afterdischarge. The present study shows a significant and selective decrease of somatostatin-1 receptor binding sites in the dentate gyrus of kindled rats. This is part of the plastic changes induced by kindling and may contribute to the increased sensitivity for the induction of generalized seizures during kindling.
采用生长抑素sst1 - sst5受体信使核糖核酸选择性寡核苷酸探针进行原位杂交组织化学，并使用[125I]酪胺酸3 - 奥曲肽、[亮氨酸2，D - 色氨酸22，125I - 酪胺酸25]生长抑素 - 28和[125I]CGP 23996（[125I]环[天冬酰胺 - 赖氨酸 - 天冬酰胺 - 苯丙氨酸 - 苯丙氨酸 - 色氨酸 - 赖氨酸 - 苏氨酸 - 酪胺酸 - 苏氨酸 - 丝氨酸]）进行定量受体放射自显影结合研究，以确定成年大鼠在背侧海马体电点燃后，海马结构、边缘系统和大脑皮质中生长抑素受体信使核糖核酸的表达水平以及受体结合位点。在对照大鼠（植入电极但未电刺激）中，生长抑素 - 1受体选择性的[125I]酪胺酸3 - 奥曲肽和非亚型选择性的[亮氨酸3，D - 色氨酸22，125I - 酪胺酸25]生长抑素 - 28优先标记海马体CA1亚区的原层和放射层、齿状回的分子层、海马结构的下托和前下托、额叶皮质的内层以及杏仁核的外侧核和基底外侧核。非亚型选择性放射性配体[125I]CGP 23996（在5 mM Mg2 +缓冲液中）优先标记海马体CA1亚区的原层和放射层、杏仁核的下托和基底外侧核。在主要标记生长抑素 - 2受体的条件下，[125I]CGP 23996（在120 mM Na +缓冲液中）在海马体CA1亚区的原层和放射层以及额叶皮质中显示出强结合，而齿状回、下托和杏仁核仅显示出弱信号。在点燃期间和点燃后，海马体的同侧和对侧之间未观察到显著差异。在第2阶段（惊厥前期）以及第5阶段（全身性运动性癫痫发作）后1周而非1个月时，所有放射性配体（除了在Na +缓冲液中的[125I]CGP 23996，其未标记该区域）均显示齿状回分子层中的生长抑素受体结合位点显著减少（约40%）。与生长抑素受体结合情况相反，在第2阶段或第5阶段均未发现sst1 - sst5受体的信使核糖核酸水平有改变。同样，在经历单次放电的大鼠大脑中，未观察到受体结合或信使核糖核酸水平的变化。本研究表明，点燃大鼠齿状回中生长抑素 - 1受体结合位点显著且选择性减少。这是点燃诱导的可塑性变化的一部分，可能有助于在点燃期间对全身性癫痫发作诱导的敏感性增加。
