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Effects of Water-Extracts of Bambusae concretio silicae(BCS, 天竺黃) on the Expression of Neurotransmitter Receptors

천죽황(Bambusae concretio silicae, 天竺黃) 물추출물이 신경전달물질 수용체의 표현에 미치는 영향

  • Yoon, Jae-Hong (Graduate School of Oriental Medicine, Dong-Guk University) ;
  • Kim, Kyung-Min (Graduate School of Oriental Medicine, Dong-Guk University) ;
  • Kim, Kyung-Hun (Graduate School of Oriental Medicine, Dong-Guk University) ;
  • Shin, Gil-Cho (Graduate School of Oriental Medicine, Dong-Guk University) ;
  • Jeong, Seung-Hyun (Graduate School of Oriental Medicine, Dong-Guk University)
  • 윤재홍 (동국대학교 한의과대학 대학원) ;
  • 김경민 (동국대학교 한의과대학 대학원) ;
  • 김경훈 (동국대학교 한의과대학 대학원) ;
  • 신길조 (동국대학교 한의과대학 대학원) ;
  • 정승현 (동국대학교 한의과대학 대학원)
  • Received : 2011.06.04
  • Accepted : 2011.06.13
  • Published : 2011.06.30

Abstract

Objectives : BCS(Bambusae concretio silicae) is used as a traditional medicine in Korea for the incipient stroke. Recent reports indicated that BCS has a neuroprotective effect by anti-convulsion effect. However, it's mechanism is not well studied. The purpose of this study was to investigate into the molecular mechanism of BCS for neuroprotection in normoxia of cultured rat hippocampal neurons. Methods : BCS (1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$) was added to culture media (Neurobasal supplemented with B27) on DIV 0, given a normoxia, and the cell viability was measured by typical phase-contrast images of the cultures with 1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$ on DIV 21. Effects of BCS on the expression of various synaptic proteins ($GABA_B$ R1, $GABA_B$ R2, GlyR, PSD95) were observed by immunocytochemistry showing on DIV 3, 7 and 21. Results : Typical phase-contrast images of the cultures indicated that BCS has a protective effect of rat hippocampal cells in normoxia. The BCS upregulated $GABA_B$ R1 after normoxia on DIV 7, $GABA_A$ ${\beta}2/3$ on DIV 21 and $GABA_B$ R2 on DIV 21. And the BCS downregulated PSD95 after normoxia on DIV 7. Conclusions : The present study showed evidence for the efficacy of BCS in Typical phase-contrast images, upregulation of inhibitory neurotransmitter receptors($GABA_B$ R1) and downregulation of PSD95 which eventually protected neuronal cell death in normoxia.

Keywords

References

  1. Curtis DR, Johnston GA. Amino acid transmitters in the mammalian central nervous system. Ergeb Physiol. 1974;69:97-188.
  2. Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochem. 1984;42:1-11. https://doi.org/10.1111/j.1471-4159.1984.tb09689.x
  3. Curtis DR, Duggan AW, Felix D, Johnston GA. GABA, bicuculline and central inhibition. Nature. 1970;226(5252):1222-4. https://doi.org/10.1038/2261222a0
  4. Krnjevic K, Phillis JW. Iontophoretic studies of neurones in the mammalian cerebral cortex. J. Physiol. 1963;165:274-304. https://doi.org/10.1113/jphysiol.1963.sp007057
  5. Farrant M, Kaila K. The cellular, molecular and ionic basis of GABAA receptor signalling. Prog Brain Res. 2007;160:59-87. https://doi.org/10.1016/S0079-6123(06)60005-8
  6. 전국한의과대학 본초학교수 공편저. 본초학. 서울:영림사. 1999:466.
  7. 新文豐出版公司. 新編 中藥大辭典. 中國:新文豐出版公司. 1981:793.
  8. 신민교. 임상본초학. 서울:영림사. 1997:761.
  9. 원광대학교 제21기. 本草求眞. 전북:木과 水. 1999:535.
  10. 李梴. 국역 편주의학입문. 서울:남산당. 1981:264.
  11. 조정숙, 양재하, 박창국, 이희순, 김영호. 뇌졸중 치료 생약 추출물의 흥분성 신경독성 억제효과. 약학회지. 2000;44(1):29-35.
  12. 서영준, 정지천. 신경세포에서 천죽황과 페놀성 물질의 항산화 및 신경보호 효과. 대한한방내과학회지. 2000;21(2):219-25.
  13. 정지천, 이우헌. 흰쥐 astrocyte에 있어서 amyloid-$\beta$에 의한 독성과 지질과산화에 미치는 천죽황의 영향. 대한한방내과학회지. 1998;19(2):381-91.
  14. HJ Ji, SI Lee. Hanyack-Gyugyuk-Juhea. Seoul:Korean index Co. 2007.
  15. Brewer GJ, Torricelli JR, Evege EK, Price PJ. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. J. Neurosci Res. 1993;35:567-676. https://doi.org/10.1002/jnr.490350513
  16. LeDoux, Joseph 저, 강봉균 역. 시냅스와 자아. 서울:소소. 2005:104-5.
  17. Galanopoulou AS. GABA(A) Receptors in Normal Development and Seizures: Friends or Foes? Curr Neuropharmacol. 2008;6(1):1-20. https://doi.org/10.2174/157015908783769653
  18. Drewe JA, Chen JS, Reyes AA, Lan NC. Stable high expression of human gamma-aminobutyric acidA receptors composed of alpha and beta subunits. Life Sci. 1995;57(12):1175-82. https://doi.org/10.1016/0024-3205(95)02063-O
  19. Pritchett DB, Sontheimer H, Gorman CM, Kettenmann H, Seeburg PH, Schofield PR. Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits. Science. 1988;242(4883):1306-8. https://doi.org/10.1126/science.2848320
  20. Loup F, Wieser HG, Yonekawa Y, Aguzzi A, Fritschy JM. Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy. J. Neurosci. 2000;20(14):5401-19.
  21. Mintz IM, Bean BP. GABAB receptor inhibition of P-type $Ca^{2+}$channels in central neurons. Neuron. 1993;10:889-98. https://doi.org/10.1016/0896-6273(93)90204-5
  22. Thompson SM, Capogna M, Scanziani M. Presynaptic inhibition in the hippocampus. Trends Neurosci. 1993;16:222-7. https://doi.org/10.1016/0166-2236(93)90160-N
  23. Poncer JC, McKinney RA, Gahwiler BH, Thompson SM. Either N- or P-type calcium channels mediate GABA release at distinct hippocampal inhibitory synapses. Neuron. 1997;18:463-72. https://doi.org/10.1016/S0896-6273(00)81246-5
  24. Luscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA. G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron. 1997;19:687-95. https://doi.org/10.1016/S0896-6273(00)80381-5
  25. Bettler B, Kaupmanna K, Bowery N. GABAB receptors: drugs meet clones. Current Opinion in Neurobiology. 1998;8(3):345-50. https://doi.org/10.1016/S0959-4388(98)80059-7
  26. Marchall FH, White J, Mailn M, Green A, Wise A. GABAB receptors function as heterodimers. Biochem Soc Trans. 1999Aug;27(4):530-5. https://doi.org/10.1042/bst0270530
  27. Hill DR. GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br J Pharmacol. 1985;84:249-57.
  28. Steiger JL, Bandyopadhyay S, Farb DH, Russek SJ. cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. J Neurosci. 2004;24:6115-26. https://doi.org/10.1523/JNEUROSCI.1200-04.2004
  29. Diverse-Pierluissi M, Remmers AE, Neubig RR, Dunlap K. Novel form of crosstalk between G protein and tyrosine kinase pathways. Proc Natl Acad Sci USA. 1997;94:5417-21. https://doi.org/10.1073/pnas.94.10.5417
  30. Couve A, Thomas P, Calver AR, Hirst WD, Pangalos MN, Walsh FS, et al. Cyclic AMP-dependent protein kinase phosphorylation facilitates GABAB receptor-effector coupling. Nat Neurosci. 2002;5:415-24.
  31. Ren X, Mody I. Gamma-hydroxybutyrate reduces mitogenactivated protein kinase phosphorylation via GABAB receptor activation in mouse frontal cortex and hippocampus. J Biol Chem. 2003;278:42006-11. https://doi.org/10.1074/jbc.M304238200
  32. Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M. et al., International union of pharmacology; XXXIII. Mammalian $\gamma$-aminobutyric acid B receptors: structure and function, Pharmacol Rev 54 2002;247-64. https://doi.org/10.1124/pr.54.2.247
  33. Calver AR, Davis CH, Pangalos MN. GABAB receptors: from monogamy to promiscuity, Neurosignals 11 2002;299-314. https://doi.org/10.1159/000068257
  34. Liu QR, Lopez-Corcuera B. Mandiyan S, et al. Cloning and expression of a spinalcord- and brain-specific glycine transporter with novel structural features. J Biol Chem. 1993;268:22802-8.
  35. Jursky F, Nelson N. Localization of glycine neurotransmitter transporter (GLY2) reveals correlation with the distribution of glycine receptor. J Neurochem. 1995;64:1026-33.
  36. Kim XM, kingsmore SF, Han H. et al. Cloning of the human glycine transporter type 1:molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes. Mol Phamacol. 1995;45:608-17.
  37. 김석열. 선퇴(Cryptotympana pustulata Fabricus, 蟬退) 물추출물이 배양한 흰쥐 해마신경세포의 신경전달물질 수용체의 표현에 미치는 영향. 동국대학교 대학원. 2009:1-29.
  38. 서종훈, 김동현, 이동웅, 김근우, 구병수. 가미희첨환(加味稀僉丸)이 GABA성(性) 신경전달에 미치는 영향에 관한 연구. 동의신경정신과학회지. 2008;19(1):43-54.
  39. 김성욱, 공대종, 안현국, 김근우, 구병수. 천마전헐탕의 신경수용체 효능활성에 관한 연구. 동의신경정신과학회지. 2004;15(1):77-86.
  40. 최윤희, 정지욱. Elevated Plus-Maze를 이용한 현삼의 항불안 효과: GABA 신경계와의 관련성 연구. 동의생리병리학회지. 2010;24(3):476-83.