Lovastatin and nicotine modulate α7 and α4β2 acetylcholine nicotinic receptors

BORRONI M.V; KAMEERBECK C.B; PEDICONI M.F.; BARRANTES F.J

C.A.B.A.

Congreso; Molecular mechanisms in cell signaling and gene expression; 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (AChR) subtypes found in central synapses and in the hippocampus in particular. The effects of lovastatin (an inhibitor of cholesterol biosynthesis, 10-1000 nM) and nicotine (a general AChR agonist, 1-100 μM) were evaluated on these two AChRs endogenously expressed in rat hippocampal neurons. Chronic (14 days) lovastatin and nicotine treatment augmented cell-surface levels of α7 and α4β2 neuronal AChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein levels as determined by Western blots. α4β2 AChR levels in neurites were more sensitive to nicotine than those in soma, at all concentrations tested. The opposite was the case with α7 AChRs. At low lovastatin concentrations (10-100 nM), the increase in neurite α4β2 AChR was higher than in soma; the opposite occurred at higher (500-1000 nM) lovastatin concentrations. However, neurite α7 AChRs rose more than somatic α7 AChRs at all lovastatin concentrations tested. These results suggest that α7 and α4β2 AChR are regulated in hippocampal neurons by cholesterol levels and agonist exposure. This regulation depends on drug concentration and receptor localization.