Functional Nicotinic Acetylcholine Receptors Are Expressed in B Lymphocyte-Derived Cell Lines

Abstract

Nicotine has been shown to affect B lymphocyte immune response. In this study, we have explored the presence of nicotinic receptors in B lymphocyte-derived cell lines, myeloma X63-Ag8 and hybridoma 1D6. We found that myeloma expressed on average 10,170 Ϯ 1,100 [ 3 H]epibatidine and 6,730 Ϯ 370 125 I-␣-bungarotoxin binding sites per cell, thus reflecting the presence of both homomeric and heteromeric nicotinic receptors. More specifically, the presence of ␣4-and ␣7-containing nicotinic receptor subunits was demonstrated in both myeloma and hybridoma cells with subunit-specific antibodies. It was significantly higher in dividing than in resting cells. Long-term exposure to nicotine, at physiological concentration found in smokers, resulted in up-regulation of both ␣4 and ␣7 subunits in hybridoma cells. Additionally, nicotine stimulated hybridoma cell proliferation, whereas it decreased antibody production. In contrast, ␣7-specific snake toxins inhibited cell proliferation but increased antibody production. It is concluded that myeloma and hybridoma cells express ␣4-and ␣7-containing nicotinic receptors, which participate in regulating cell proliferation and function.

Long-Term Exposure to Nicotine Modulates the Level and Activity of Acetylcholine Receptors in White Blood Cells of Smokers and Model Mice

“…In addition to its effects on the central nervous system, nicotine is known to affect many other tissues such as the respiratory tract, skin, and vascular and immune tissues (Grando et al, 1995;Macklin et al, 1998;Maus et al, 1998;Sato et al, 1999). Furthermore, nAChRs have already been found in lymphocytes (Skok et al, 2003) as well as in polymorphonuclear (PMN) leukocytes (Benhammou et al, 2000). In this context, we sought to investigate the regulation of nAChRs in blood cells of smokers and of wild-type (WT) and nAChR knockout mice continually administered nicotine.…”

Editorial: To channel or not to channel? Functioning of nicotinic acetylcholine receptors in leukocytes

“…The lymphocytes contain much more nicotine/epibatidine-binding sites per cell (ϳ10 4 [8]) than epithelial (630) or endothelial (990) cells, where the ion channel activity has been demonstrated [5,6]; therefore, the absence of ion currents cannot be a result of the low receptor density. One of the possible explanations is that nAChRs exposed in lymphocytes/leukocytes are in a desensitized state mainly, because of constant low acetylcholine concentration found in the blood or their close contacts with adjacent membrane structures.…”

“…Similarly, nicotine induces intracellular Ca 2ϩ fluxes in ␣7 nAChR-expressing T lymphocytes [2] and favors proliferation of B lymphocytes [8] without detectable ion channel activity. These data allow suggesting that the ␣7 ion channel permeability plays a minor role (if any) in stimulating intracellular events to support cell survival or activation.…”

The Pharmacological Actions of Nicotine on the Gastrointestinal Tract

“…In addition, the expression of nicotinic receptor was found to correlate with cell proliferation, and long-term exposure to nicotine could up-regulate both the expression of a 4 and a7 subunits (79). Interestingly, our recent results also show that nicotine can significantly up-regulate mRNA levels of the a 7 subunit of nicotinic receptor in a colon cancer line.…”