(−)Nicotine inhibits the activations of phospholipases A2 and D by amyloid β peptide

It has been established that amyloid beta peptide (AβP) activates phospholipase A2, phospholipase C and phospholipase D of LA-N-2 cells and other cell types. Nicotine in addition to being a cholinergic agonist, may be neuroprotective. We have investigated the ability of (−)nicotine to blunt the phospholipase activations by AβP in LA-N-2 cells. (−)Nicotine inhibits the AβP activation of phospholipase A2, with an IC₅₀ of 76 μM and of phospholipase D with an IC₅₀ of 252 μM. (−)Nicotine did not blunt the AβP activation of phospholipase C. These inhibitions of AβP activations were not observed with (+)nicotine or cotinine. The (−)nicotine inhibition of AβP activation of these two phospholipases was unaffected by hexamethonium and D-tubocurarine. There was no inhibition of the phospholipase A2 activity present in homogenates of LA-N-2 cells. Exposure of LA-N-2 cells to (−)nicotine for 2 h resulted in the blockade of phospholipase A2 activation by kainate and AβP but did not affect the ability of quisqualate and AβP to activate phospholipase D. These data suggest that if the nicotine inhibition of AβP activations is receptor occupancy mediated then it is by an atypical receptor type.