MK-801, a non-competitive NMDA receptor antagonist, prevents postischemic decrease of inositol 1,4,5-trisphosphate receptor mRNA expression in mongolian gerbil brain Chang-Sub Uhm a, *, Young-Suk Suh a , Joo-Bae Park b , Moon Bang Sohn a , Im Joo Rhyu a , Hyun Kim a a Institute of Human Genetics and Department of Anatomy, Korea University College of Medicine, 126-1 Anam-Dong 5-Ga, Seongbuk-Ku, Seoul, 136–705 South Korea b Department of Biochemistry, Seoul National University College of Medicine, 28 Yongondong, Chongrogu, Seoul, 110–799 South Korea Received 13 July 1998; received in revised form 17 August 1998; accepted 3 September 1998 Abstract Changes of inositol 1,4,5-trisphosphate receptor (IP 3 R) mRNA expression after transient brain ischemia and the effect of MK- 801, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, on the IP 3 R mRNA expression was studied in mongolian gerbil brain by in situ hybridization. Transient ischemia was induced by ligating left common carotid artery for 10 min, and the animals were allowed recovery from 15 min to 24 h. MK-801 was introduced intraperitoneally 30 min before ischemia. IP 3 R mRNA expression was decreased in dentate gyrus and hippocampus from 90 min until 24 h after ischemia. MK-801 pretreatment prevented the change of IP 3 R mRNA expression after ischemia. These results suggest that IP 3 R mRNA expression in ischemia may be related with NMDA receptor.  1998 Elsevier Science Ireland Ltd. All rights reserved Keywords: In situ hybridization; IP 3 receptor; Ischemia; MK-801; Mongolian gerbil; N-Methyl-D-aspartic acid receptor Brain ischemia due to cerebrovascular occlusion changes the cellular and metabolic processes leading to neuronal death [16]. Several reports indicate that perturbation of neu- ronal calcium homeostasis caused by excitatory amino acid such as glutamate may play an important role in the ische- mia-induced neuronal death [1]. NMDA induced the forma- tion of inositol 1,4,5-trisphosphate (IP 3 ) in a culture of chick retina cells, which was blocked by MK-801 [19]. Recently Zhang et al. [20] reported the decreased IP 3 R mRNA ex- pression after transient ischemia in rat brain. However, the clear relationship between NMDA receptor and secondary messenger system including IP 3 R especially in the ischemic insult has not been settled yet. To answer this question, the authors investigated time-course changes of IP 3 R mRNA expression in the mongolian gerbil brain after transient ischemia with or without MK-801 pretreatment by in situ hybridization. We also evaluated the changes of heat shock protein (hsp) 70 and v-fos mRNA expression in the adjacent sections to make sure that ischemic treatments were done properly, taking advantage of the published data on changes of gene expression in ischemic gerbil brain [18]. Total 67 male mongolian gerbil of 60–80 g in weight were used. Animals were kept warm with a hot pad during the MK-801 and ischemic treatments. After anesthesia with intraperitoneal injection of Nembutal (50 mg/kg body weight), blood flow to left brain was blocked by ligating left common carotid artery with silk thread for 10 min, and then, the animals were allowed to recover. Just after remov- ing silk thread, and after 15, 30, 90 min, 4, 6, and 24 h, the animals were sacrificed by decapitation, the brains were removed quickly and were frozen in isopentane pre-cooled with dry ice. Right brain of each animal was used as an internal control. In addition, three sham-operated animals were prepared in the same way except for the ligation of left common carotid artery. To study the effect of MK-801, Neuroscience Letters 255 (1998) 111–114 0304-3940/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00727-7 * Corresponding author. Tel.: +82 2 9206150; fax: +82 2 9295696; e-mail: uhmcs@kuccnx.korea.ac.kr.