| 백서 대뇌피질절편에서 산소 및 포도당 결핍에 의한 [3H]Acetylcholine의 유리에 관한 연구 |
| 이정주, 김기원***·서만욱**·김영현** |
| 전북대학교 의과대학 신경과학교실, 약리학교실* 및 의과학 연구소** |
| Study on the [3H]Acetylcholine Release Induced by Oxygen-Glucose Deprivation in Rat Cerebral Cortical Slices |
| Jeong-Ju Lee, M.D., Kee-Won Kim, M.D.***, Man-Wook Seo, M.D.**, Young-Hyun Kim, M.D.** |
| Department of Neurology and Pharmacology* and Institute for Medical Sciences**, Medical School, Chonbuk National University |
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| Abstract |
Background: It has been shown that cerebral ischemia alters brain acetylcholine (Ach) metabolism. In an attempt to elucidate the mechanisms for ischemia-induced release of Ach in vitro, the effects of drugs which can influence the cholinergic neurotransmission on the ischemia-induced release of [3H]Ach from cerebral cortical slices of the rat were examined.
Methods: The cortices of decapitated rats were chopped and dispersed in artificial CSF. Then, the tissue suspensions were incubated with [3H]choline. The tissues were transferred and incubated in washing, hypoglycemic (deprivation of glucose), ischemic (deprivation of oxygen and glucose) and extracting plates sequently. Ischemia-induced release of [3H]Ach was expressed as percentage of the total [3H]Ach present in the slices.
Results: Ischemia induced significant release (about 9.3% of total tissue content) of [3H]Ach from cerebral cortical slices in vitro. This [3H]Ach release was significantly attenuated by tetrodotoxin, a voltage-sensitive Na+-channel blocker, and Mg2+, a physiological N-methyl-D-aspartate (NMDA) receptor blocker. Vesamicol (1 M), a blocker of vesicular transport of Ach, MK-801 and ketamine, NMDA receptor antagonists, 6,7-nitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainate/AMPA receptor antagonists, and 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX), a AMPA receptor blocker attenuated the [3H]Ach. Nitrendipine, nimodipine, inhibitor of L-type Ca2+ channels, and -conotoxin GVIA, an inhibitor of N-type Ca2+ channels, significantly attenuated the ischemia-induced release of [3H]Ach. Omission of Ca2+ from incubation media attenuated the ischemia-induced [3H]Ach release. Inhibitors of intracellular Ca2+ release, dantrolene and TMB-8, and a cell-permeable calcium chelator, 1,2-bis (2-aminophenoxy)-ethane-N, N, N+, N+-tetraacetic acid tetrakis (acetoxymethyl) ester (BAPTA-AM), inhibited the ischemia-evoked [3H]Ach release.
Conclusion: These results suggest that the ischemia can induce Ach rele
Key Words: [3H]Ach release, cerebral cortical slices, ischemia |
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