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1988 Fiscal Year Final Research Report Summary

Action mechanisms of antiepileptic drugs in relation to cellular lipids

Research Project

Project/Area Number 60440052
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionNational Institute of Neuroscience, N C N P

Principal Investigator

IMAZAWA Masaoki  Division of Neurochemistry, 神経研究所・代謝研究部 (90158767)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Kazuyuki  Division of Neurochemistry, 神経研究所・代謝研究部, 研究員 (50175494)
Project Period (FY) 1985 – 1988
Keywordscellular lipids / antiepileptic drugs / phenytoin / inositide response / cyclic GMP / IP_3 receptor
Research Abstract

The specific binding sites for phenytoin (PHT) were found to exist in the membrane fractions of rat brain. The binding activity of the sites was found to be suppressed by cellular lipids, tri- and di-phosphoinositides. Inositide response was determined using a slice experiment of rat brain cortex on the basis of the Berridge's method. Among the compounds tested which may be associated with seizure, carbachol, norepinephrine (NE) and a high concentration of potassium were observed to markedly stimulate the response. On the other hand, no stimulation was shown with pentylenetetrazol. No effects of antiepileptic drugs were observed on the stimulated response which occurred with carbachol.
The cyclic GMP (cGMP) levels were raised by various excitatory substances, e.g. excitatory amino acids (glutamate, NMDA, ibotenate), carbachol, a high concentration of potassium, and somatostatin. No changes in the cGMP levels were observed by inhibitory, substances, e.g. NE and GABA. The cAMP levels demo … More nstrated no such a tendency in parallele with excitatory substances. All the elevated cGMP levels with the excitatory substances were suppressed by pentylenetetrazol. It is likely that the cGMP levels are associated with occurring seizures and the function of pentylenetetrazol remains to be elucidated.
Effects of antiepileptics and Ca-channel antagonists on inositol trisphosphate (IP_3; a putative second messenger yielded from triphosphoinositides) binding and IP_3-induced ca release were examined. Antiepileptics (PHT, valproate) and Ca-channel antagonists (verapamil, diltiazm, flunarizine, nicardipine, cinnarizine), examined, did not significantly inhibit the IP_3-receptor binding. On the other hand, PHT, phenobarbital, carbamazepine inhibited the Ca-releasing activity of IP_3 in the cerebellar membrane fractions by approx. 20% at therapeutic concentrations. As the findings here seem to indicate divergent features of the IP_3 receptor, further work using microsomal fractions of purified receptor preparations will be required. Less

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Miyamoto K;Taguchi F;Imazawa M: Jpn J Psychiat Neurol. 40. 357-360 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto K;Yamagami S: Jpn J Psychiat Neurol. 40. 371-373 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe K;Kogure K;Yamamoto H;Imazawa M;Miyamoto K: J Neurochem. 48. 503-509 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto K;Ogawa N: Jpn J psychiat Neurol. 41. 377-379 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto K;Taguchi F;Imazawa M: Jpn J Psychiat Neurol. 41. 387-389 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imazawa M;Kabuto Y;Miyamoto K;Nishimura S;Yagi K: Jpn J Psychiat Neurol. 43. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮本侃治: "「生化学的精神医学」てんかん" 星和書店, 459 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清野昌一,宮本侃治: "「てんかん薬剤治療の実際」抗てんかん薬治療の基磯ー血中濃度を中心として" 大日本製薬, 307 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyamoto,K.; Taguchi,F; Imazawa,M:"Correlation between inositide response and seizure-related substances as well as antiepileptic drugs" Jpn J Psychiat Neurol. 40. 357-360 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyamoto,K; Yamagami,S:"Approaches to epilepsy via biological chemistry-currently applicable approaching methods to epilepsy" Jpn J Psychiat Neurol. 40. 371-373 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe,K; Kogure,K; Yamamoto,H; Imazawa,M; Miyamoto,K:"Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex" J Neurochem. 40. 503-509 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyamoto,K; Ogawa,N:"Approaches to epilepsy via biological chemistry-A step toward elucidating the biochemical mechanisms of epileptic seizures" Jpn J Psychiat Neurol. 41. 377-379 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyamoto,K; Taguchi,F; Imazawa,M:"Effects of various seizure-associated compounds on biochemical functions related to inositide cycle" Jpn J Psychiat Neurol. 41. 387-389 (1987)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1990-03-20  

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