| Project/Area Number |
14370037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyoritsu University of Pharmaceutical Sciences |
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Principal Investigator |
KAWASHIMA Koichiro Kyoritsu University of Pharmaceutical Sciences, Pharmacology, Professor, 薬学部, 教授 (70095008)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Takeshi Kyoritsu University of Pharmaceutical Sciences, Department of Pharmacology, Associate Professor, 薬学部, 助教授 (80255380)
FUJIMOTO Kazuko Kyoritsu University of Pharmaceutical Sciences, Department of Pharmacology, Research Associate, 薬学部, 助手 (50229043)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | acetylcholine (ACh) / lymphocyte / mAChR / nAChR / choline acetyltransferase (ChAT) / high affinity choline transporter / acetylcholinesterase / nitric oxide / M5 KOマウス / MRL / 1pr / プロスタグランディンE2 / ノックアウトマウス / lprマウス / プロスタグランディンE_2 |
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| Research Abstract |
Acetylcholine(ACh) is well known as a neurotransmitter in the central and peripheral nervous systems in mammalian species. Both muscarinic and nicotinic ACh receptors(mAChRs and nAChRs, respectively) have been identified in lymphocytes, and their stimulation by mAChR and nAChR agonists elicits a variety of functional and biochemical effects. On the basis of these findings, it has been postulated that the parasympathetic nervous system may play a role in immune-neurohumoral crosstalk. However, we discovered that lymphocytes express most components of the cholinergic system, such as various subtypes of mAChRs and nAChRs, ACh, choline acetyltransferase(ChAT), high affinity choline transporter and acetylcholinesterase. Furthermore, we have observed that ACh and mAChR agonists elicit intracellular Ca^<2+> signaling, up-regulation of c-fos expression and nitric oxide synthesis within T and B cells, probably via M_3 and M_5 mAChRs. Stimulation of nAChRs with ACh or nicotine caused rapid and transient Ca^<2+> signaling in T and B cells, probably via α7 nAChR subunit-mediated pathways. Phytohemagglutinin- or antigen-induced T cell activation via cell surface molecules(e.g., T cell receptor/CD3 complexes) enhances lymphocytic cholinergic transmission by up-regulating ChAT and M_5 mAChR expression, suggesting that a local lymphocytic cholinergic system is involved in regulating immune function. This idea is supported by the findings that lymphocytic cholinergic activity is altered in animal models exhibiting immunological abnormalities. In addition, it appears likely that during interactions mediated by cell surface molecules T cells communicate via ACh with thymic epithelial cells and vascular endothelial cells, which also express ChAT and nAChRs or mAChRs. Collectively, the data we obtained provide a compelling picture in which lymphocytes constitute a cholinergic system that is independent of cholinergic nerves, and which is involved in the regulation of immune function.
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