Rol del receptor nicotínico alfa 7 en la activación de linfocitos humanos

DE ROSA, M.J.; DIONISIO, L.; BOUZAT, C.; ESANDI, M.C.

Buenos Aires

Congreso; X Congreso PABMB - XLI Reunión Anual SAIB - XX Reunión Anual SAN; 2005

The neuronal nicotinic receptor alpha 7 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 alpha 7 in lymphocytes after phytohemagglutinin (PHA) activation. alpha 7 mRNA was detected in lymphocytes incubated for 48 hrs in the presence of PHA or PHA + bungarotoxin (BTX), an alpha 7 antagonist. The modulation of lymphocyte activation by alpha 7 was evaluated by measuring cell proliferation using 3H-thymidine 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 alpha 7 by BTX modulates ACh synthesis, and this event could affect lymphocyte activation through mAChRs.