The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

Nasir Hussin Ameer; Jae Hee Lee; Myoung Ae Choi; Guang-Shi Jin; Min Sun Kim; Byung Rim Park

doi:10.4196/kjpp.2010.14.3.151

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Ameer, Lee, Choi, Jin, Kim, and Park: The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

Original Article

Korean J Physiol Pharmacol 2010;14(3):151-156.

Published online: 18 February 2010

DOI: https://doi.org/10.4196/kjpp.2010.14.3.151

The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

Nasir Hussin Ameer¹, Jae Hee Lee¹, Myoung Ae Choi¹, Guang-Shi Jin², Min Sun Kim¹, Byung Rim Park^1,

¹Department of Physiology, Wonkwang University School of Medicine, and Brain Research Institute at Wonkwang University, Iksan 570-749, Korea

²Department of Neurosurgery, Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China

Corresponding to: Byung Rim Park, Department of Physiology, Wonkwang University School of Medicine, 344-2, Shinyong-dong, Iksan 570-749, Korea. (Tel) 82-63-850-6773, (Fax) 82-63-852-6108, (E-mail) byungp@wku.ac.kr

Received 4 May 2010 Revised 20 May 2010 Accepted 26 May 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was 66.3±7.5% and 62.3±5.7% 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to 39.0±3.5% and 47.0±5.1% at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was 5.6±0.4 and 5.2±0.9 at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to 2.9±0.8 and 3.0±0.3 at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to 35.9±5.2%, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to 28.8±9.5%. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to 11.8±3.2%, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

Keywords: Glutamate, Insular cortex, Intestinal transit, MCAO, MK-801

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Fig. 1.

Changes in intestinal motility 2 and 12 h after MCAO. Sham, the common carotid artery, internal carotid artery and external carotid artery in the right side were exposed through a midline incision of the neck and the incision of the skin was sutured; MCAO, middle cerebral artery occlusion; IT, intestinal transit; GC, geometric center; Post-op, time after MCAO. The number of animals was 7 in each session of each group. Values are mean±SD. ^∗∗Significant differences between Sham and MCAO (^∗∗p<0.01).

Fig. 2.

Effect of MK-801 on intestinal motility after MCAO. Intestinal transit was measured 2 h after injection or surgery. Saline, intraperitoneal injection of sterile saline solution (1.0 ml/kg) in control animals; MCAO, middle cerebral artery occlusion; Atropine, intraperitoneal injection of atropine sulfate in control animals; MK-801, intraperitoneal injection of MK-801 in control animals; MK-MCAO, pretreatment with MK-801 in MCAO. The number of animals was 5 in each group, except MCAO group (n=7, data from Fig. 1). Values are mean±SD. ^∗∗Significant differences from Saline (^∗∗p<0.01). ^†Significant differences from MCAO (^†p<0.05, ^‡p<0.01).

Fig. 3.

Effect of MK-801 on expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO. MCAO, middle cerebral artery occlusion; MK-MCAO, pretreatment with MK-801 in MCAO. The number of animals was 5 in each group. Values are mean±SD. ^∗∗Significant differences between MCAO and MK-MCAO (^∗∗p<0.01).

Fig. 4.

Photomicrographs of c-Fos protein expression in the bilateral insular cortex and cingulate cortex 2 h after MCAO. MCAO, middle cerebral artery occlusion; MK-MCAO, pretreatment with MK-801 in MCAO; IPSI, ipsilateral to the occlusion; CONT, contralateral to the occlusion. Scale bar: 200 μm.

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