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2000 Fiscal Year Final Research Report Summary

Effect of nicotine administration on development of muscarinic receptor in central nervous system of rat neonate

Research Project

Project/Area Number 11670084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionFukui Medical University

Principal Investigator

TANIGUCHI Takanobu  Fukui Medical University, Department of Pharmacology Associate Professor, 医学部, 助教授 (60217130)

Co-Investigator(Kenkyū-buntansha) MURAMATSU Ikunobu  Fukui Medical University, Department of Pharmacology Professor, 医学部, 教授 (10111965)
Project Period (FY) 1999 – 2000
KeywordsNicotine / Muscarinic receptor / Choline transporter / Rat neonate brain / Development
Research Abstract

Rat fetuses or neonates were exposed to nicotine by administering nicotine to pregnant or lactating dams to estimate effects of nicotine on the development of cholinergic nervous system in brain of rat neonates. Since up-regulation of nicotinic receptor in rat neonates by nicotine administration has been already shown, we focussed on muscarinic receptor.
1) We employed [^3H] QNB as a ligand to estimate muscarinic receptor. The level of muscarinic receptor in cerebral cortex started to develop just after birth and linearly increased to reach adult level 5 weeks after birth. Cerebellum showed a similar time course of muscarinic receptor development. However, in midbrain and hippocampus the level reached 80 % and in brainstem it reached 100 % of the adult level at 2 weeks after birth.
2) We used pirenzepine as M1 specific and AF-DX116 as M2 specific ligands to examine the proportion of subtype of muscarinic receptor. Cerebral cortex and hippocampus were M1 dominant whereas cerebellum, midbrain and brainstem were M2 dominant tissues.
3) We investigated the development of choline transporter, which is a specific marker for cholinergic post-synaptic terminal, by using [^3H] hemicholinium-3. Choline transporter in cerebral cortex started to develop after birth and reached 80 % of the adult level at 2 weeks after birth, as similarly seen in muscarinic receptor development in midbrain or hippocampus.
4) Nicotine administration delayed the development of muscarinic receptor in cerebral cortex and cerebellum and delayed also that of choline transporter. These delays caught up with the normal time course at 5 weeks after birth.
In conclusion, the present study demonstrates that perinatal nicotine treatment causes a developmental delay of muscarinic nervous system in rat neonates. These data can help us to understand one possible mechanism of the toxicity of cigarette smoking, as it related to brain development and the cause of neurological disorders

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] J.Zhu,T.Taniguchi,T.Tanaka,F.Suzuki and I.Muramatsu: "Effects of perinatal nicotine exposure on development of [^3H] Hemicholinium-3 binding sites in rat neonate brain"Japanese Journal of Pharmacology. 84. 32-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Zhu,T.Taniguchi,R.Takauji,F.Suzuki,T.Tanaka and I.Muramatsu: "Inverse agonism and neutral antagonism at a constitutively active alpha-1a adrenoceptor"British Journal of Pharmacology. 131. 546-552 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Zhu, T.Taniguchi, T.Tanaka, F.Suzuki, I.Muramatsu: "Effects of perinatal nicotine exposure on development of [^3H] Hemicholinium-3 binding sites in rat neonate brain."Jpn.J.Pharmacol.. 84. 32-35 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Zhu, T.Taniguchi, R.Takauji, F.Suzuki, T.Tanaka, I.Muramatsu: "Inverse agonism and neutral antagonism at a constitutively active alpha-1a adrenoceptor."Br.J.Pharmacol.. 131. 546-552 (2000)

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

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Published: 2002-03-26  

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