Neuronal alpha7 nicotinic receptors: role in the activation of human lymphocytes

DE ROSA, M.J.; DIONISIO L; CECILIA BEATRIZ BOUZAT; ESANDI MC

Pinamar

Congreso; X Panamerican Association for Biochemistry and Molecular Biology (PABMB) Congress/XLI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology/XX Annual Meeting of the Argentine Society for Neurochemistry; 2005

Panamerican Association for Biochemistry and Molecular Biology (PABMB) /Argentine Society for Biochemistry and Molecular Biology (SAIB)/Argentine Society for Neurochemistry (SAN)

The neuronal nicotinic receptor alpha7 has been shown to be present in human lymphocytes. However, little is known about its functional role. In the present study we investigated the contribution of alpha 7 to lymphocyte activation. We determined by RT-PCR the presence of alpha7 in lymphocytes after phytohemagglutinin (PHA) activation. alpha7 mRNA was detected in lymphocytes incubated for 48 hrs in the presence of PHA or PHA + bungarotoxin (BTX), an alfa7 antagonist. The modulation of lymphocyte activation by alpha7 was evaluated by measuring cell proliferation using 3H-timidine incorporation. Our results reveal that the presence of BTX during activation by PHA leads to a 2-fold increase in cell proliferation. In addition, BTX alone was unable to induce cell proliferation. Secretion of acetylcholine (ACh) and activation of muscarinic receptors (mAChRs) have been suggested to be involved in lymphocyte activation. We propose that the increment in the proliferation promoted by PHA+ BTX is due to an increase in the synthesis of ACh. To test this hypothesis, we performed RT-PCR to detect choline acetyltransferase (CHAT) mRNA after cell incubation with either PHA or BTX. The increase in CHAT, which catalizes ACh synthesis, is an indirect measurement for the increase of secreted ACh. We show that PHA and BTX induce CHAT gene expression. These results suggest that the blockade of alpha7 by BTX modulates ACh synthesis, and this event could affect lymphocyte activation through mAChRs.