Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation

Takeshi Fujii, Yoshihiro Watanabe, Kazuko Fujimoto, Koichiro Kawashima

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21 Citations (Scopus)


Although acetylcholine (ACh) is classically thought of as a neurotransmitter in mammalian species, lymphocytes possess most of the components needed to constitute an independent non-neuronal cholinergic system. These include ACh itself, choline acetyltransferase (ChAT), high-affinity choline transporter, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Activation of mAChRs and nAChRs on lymphocytes elicits increases in the intracellular Ca2+ concentration and stimulates c-fos gene expression and nitric oxide synthesis. Which subpopulations of T lymphocytes are the source of blood ACh is not yet known, though expression of ChAT mRNA was observed in human peripheral CD4+ (helper) but not in CD8+ (cytotoxic) T cells. Stimulation of lymphocytes with phytohemagglutinin, a T-cell activator, or with monoclonal antibodies that bind the CD7 and/or CD11a cell surface molecules activates lymphocytic cholinergic activity, as evidenced by increased synthesis and release of ACh and up-regulation of expression of ChAT and M5 mAChR mRNA. Abnormalities in the lymphocytic cholinergic system have been detected in spontaneously hypertensive rats and MRL-lpr mice, two animal models of immune disorders. Taken together, these data present a compelling picture in which immune function is, at least in part, under the control of an independent non-neuronal lymphocytic cholinergic system.

Original languageEnglish
Pages (from-to)373-386
Number of pages14
JournalBiogenic Amines
Issue number4-6
Publication statusPublished - 2003



  • Acetylcholine
  • CD4 T cell
  • CD8 T cell
  • Choline acetyltransferase
  • Muscarinic receptor
  • Nicotinic receptor

ASJC Scopus subject areas

  • Pharmacology
  • Neuroscience(all)

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