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

Abstract

C holinergic signaling plays an important role in inflammation and immune response. Leuko- cytes produce endogenous acetylcho- line, which affects their activation through nAChRs in an auto/paracrine way. However, the mode of nAChR sig- naling in the leukocytes is different from classical ion channel functioning in excitable (nerve and muscle) cells. Although the nAChRs expressed in he- matopoietic cells seem to be permeable for ions, the ion contribution to the nAChR signaling in these cells is mini- mal. Instead, binding of agonists or competitive antagonists affects the activ- ity of adjacent (purinergic or antigen- specific) receptors and influences the intracellular Ca2⫹ fluxes evoked by their stimulation. These data indicate that not all signaling events triggered by nAChRs require the ion channel open- ing and that ligation of the acetylcho- line-binding site induces allosteric tran- sition sufficient for certain types of re- ceptor signaling. The multiple ways of nAChR functioning in the cells of dif- ferent origin regarding the universal role of acetylcholine in living nature are discussed.