0026-895X/97/061007-08$3.00/0
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MOLECULAR PHARMACOLOGY 51:1007-1014 (1997).

Stimulatory Roles of Muscarinic Acetylcholine Receptors on T Cell Antigen Receptor/CD3 Complex-Mediated Interleukin-2 Production in Human Peripheral Blood Lymphocytes

Hiromichi Fujino, Yoshihisa Kitamura, Takeshi Yada, Takashi Uehara, and Yasuyuki Nomura

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060, Japan (H.F., Y.K., T.Y., T.U., Y.N.), and Department of Neuroscience, Research Institute for Oriental Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-01, Japan (Y.N.)

It is known that there are some bidirectional interactions between the nervous and the immune systems via neurotransmitters and cytokines. To clarify whether any neurotransmitters modulate lymphocyte functions, we examined the effects of oxotremorine-M (Oxo-M) on interleukin-2 (IL-2) production in human peripheral blood lymphocytes by using enzyme-linked immunosorbent assays, Northern blot analyses, reverse transcriptase-polymerase chain reaction, and fluorescence-activated cell sorter. Pretreatment of cells with Oxo-M (10 nM to 10 µM) for 4-24 hr enhanced phytohemagglutinin (PHA)-induced IL-2 mRNA expression and markedly increased IL-2 production compared with those induced by PHA alone. Oxo-M alone did not affect IL-2 mRNA expression and IL-2 production. In CD3-positive T cells, pretreatment with Oxo-M for 24 hr enhanced PHA-induced IL-2 production. Furthermore, pretreatment with Oxo-M enhanced PHA-induced mRNA expression of the  and  subunits of IL-2 receptors and DNA synthesis. Cytometric analysis showed Oxo-M treatment did not up-regulate expression of cell surface molecules such as CD3, CD2, CD4, CD8, and IL-2 receptors. These results suggest that activation of muscarinic receptors enhances T cell antigen receptor/CD3-induced IL-2 production.