Akiyama K, Daigen A, Yamada N, Itoh T, Kohira I, Ujike H, Otsuki S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Brain Res. 1992 Jan 8;569(1):71-7. doi: 10.1016/0006-8993(92)90370-o.
We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [3H]inositol monophosphate ([3H]InsP) was significantly increased in the AM/PC by 162 (P less than 0.0001), 130 (P less than 0.005) and 81% (P less than 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [3H]InsP was significantly increased by 55% (P less than 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1, 7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 (P less than 0.05) and 45% (P less than 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 (P less than 0.03) and 30% (P less than 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.
我们之前已经证明，在杏仁核（AM）和海马体（HIPP）点燃的大鼠的杏仁核/梨状皮质（AM/PC）中，鹅膏蕈氨酸（IBO）刺激的多磷酸肌醇（PPI）水解会长期增加。这一发现表明，PPI偶联的兴奋性氨基酸（EAA）受体功能增强可能与点燃的长期癫痫易感性有关。本研究进一步检测了代谢型EAA受体的选择性激动剂反式-ACPD以及IBO在深部梨状前皮质（DPC）点燃的大鼠脑片中诱导的PPI水解。在最后一次点燃发作后的24小时、7天和28天，IBO刺激的[3H]肌醇单磷酸（[3H]InsP）积累在AM/PC中分别显著增加了162%（P<0.0001）、130%（P<0.005）和81%（P<0.03），而在HIPP中仅在最后一次发作后的24小时显著增加，在边缘前脑（LFB）中任何时候都没有变化。在最后一次点燃发作7天后，部分点燃至平均3.7期的大鼠的AM/PC中，IBO刺激的[3H]InsP积累显著增加了55%（P<0.01），但处于1期的大鼠的AM/PC中没有增加。在最后一次点燃发作后的7天和28天，反式-ACPD刺激的PPI水解在DPC点燃的大鼠的AM/PC中分别显著增加了65%（P<0.05）和45%（P<0.005）。顺式-ACPD刺激的PPI水解在最后一次发作后的7天和28天，在DPC点燃的大鼠的AM/PC中也分别显著增加了45%（P<0.03）和30%（P<0.04）。在HIPP或LFB中，反式-ACPD或顺式-ACPD刺激的PPI水解没有增加。这些结果进一步证实了我们之前的研究，即无论点燃的主要刺激部位如何，代谢型EAA受体刺激的PPI水解在AM/PC中都表现出长期增加。
