(-)Nicotine inhibits the activations of phospholipases A2 and D by amyloid beta peptide.
It has been established that amyloid beta peptide (AbetaP) 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 AbetaP in LA-N-2 cells. (-)Nicotine inhibits the AbetaP activation of phospholipase A2, with an IC50 of 76 microM and of phospholipase D with an IC50 of 252 microM. (-)Nicotine did not blunt the AbetaP activation of phospholipase C. These inhibitions of AbetaP activations were not observed with (+)nicotine or cotinine. The (-)nicotine inhibition of AbetaP 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 AbetaP but did not affect the ability of quisqualate and AbetaP to activate phospholipase D. These data suggest that if the nicotine inhibition of AbetaP activations is receptor occupancy mediated then it is by an atypical receptor type.
Department of Biochemistry and Molecular Biology, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, MB, Canada.
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D000098:Acetophenones / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D034341:Aristolochic Acids; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003367:Cotinine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D016318:Quisqualic Acid / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D000098:Acetophenones; D016229:Amyloid beta-Peptides; D001095:Arachidonic Acids; D034341:Aristolochic Acids; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010616:Phenanthrenes; C081565:arachidonyltrifluoromethane; D018738:Hexamethonium; D009538:Nicotine; D016318:Quisqualic Acid; C000228:aristolochic acid I; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010739:Phospholipase D; D003367:Cotinine; C006821:4-bromophenacyl bromide; D007608:Kainic Acid; D014403:Tubocurarine