Relationship between the presence of alpha7 nicotinic receptor and apoptosis of human lymphocytes

M.C. ESANDI,; M.J. DE ROSA,; GARELLI, D.; D. RAYES,; CECILIA BEATRIZ BOUZAT

San Carlos de Bariloche

Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular y XXXII Reunión Anual de la Sociedad Argentina de Biofísica - Bariloche Protein Symposium, San Carlos de Bariloche; 2003

Acetylcholine (ACh) is well known as a neurotransmitter in both the central and peripheral nervous systems. ACh receptors (AChR) have been recently identified in extraneuronal cells such as those of the immune system. By using RT-PCR we have detected mRNA of a7 nicotinic receptor (AChR) in peripheral human lymphocytes after incubation with different concentrations of nicotine (10-100 μM). To determine the role of a7 in lymphocytes,  we measured the degree of apoptosis in the presence of different nicotinic ligands. The degree of apoptosis was determined by DNA cleavage forming a ladder pattern and by evaluating nuclear condensation with DAPI staining. Lymphocytes pretreated with nicotine (10-100 μM) were less susceptible to cortisol-induced apoptosis compared to untreated cells. The inhibition of apoptosis was concentration-dependent, reaching a value of 50% at 100 µM nicotine. Correlation between the presence of a7 mRNA and protection from apoptosis was always observed. Furthermore, apoptosis protection was also observed in the presence of the antagonist a-bungarotoxin. This effect might be due either to the ability of both, the antagonist and nicotine, to induce upregulation or to desensitize and block AChRs. Given that lymphocytes secrete ACh, our results suggest that these cells contain functional a7 receptors. Supported by ANPCyT, UNS, Ministerio de Salud, Fundación Antorchas and TWAS.