Takeshi Fujii1 and Koichiro Kawashima1,*
1Department of Pharmacology, Kyoritsu College of Pharmacy,
1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
*Corresponding author. FAX: +81-3-5400-2698
E-mail: kawashima-ki@kyoritsu-ph.ac.jp
Abstract: Acetylcholine (ACh) is a well characterized neurotransmitter
occurring throughout the animal kingdom. In addition, both muscarinic and
nicotinic ACh receptors have been identified on lymphocytes of various origin,
and their stimulation by muscarinic or nicotinic agonists elicits a variety
of functional and biochemical effects. It was thus initially postulated
that the parasympathetic nervous system may play a role in modulating immune
system function. However, ACh in the blood has now been localized to lymphocytes;
indeed expression of choline acetyltransferase (ChAT), an ACh synthesizing
enzyme, has been shown in human blood mononuclear leukocytes, human leukemic
T-cell lines and rat lymphocytes. Stimulation of T-lymphocytes with phytohemagglutinin
activates the lymphoid cholinergic system, as evidenced by increased synthesis
and release of ACh and increased expression of mRNAs encoding ChAT and ACh
receptors. The observation that M3 muscarinic receptor stimulation
by ACh and other agonists increases the intracellular free Ca2+
concentration and upregulates c-fos gene expression strongly argues that
ACh, synthesized and released from T-lymphocytes, acts as an autocrine and/or
paracrine factor regulating immune function. These findings present a compelling
picture in which immune function is, at least in part, under the control
of an independent lymphoid cholinergic system.
Keywords: Acetylcholine, Choline acetyltransferase, Lymphocyte, Muscarinic
receptor, Nicotinic receptor
Copyright The Japanese Pharmacological Society
[Back to TOC]