The Allosteric Potentiation of Nicotinic Acetylcholine Receptors by Galantamine Is Transduced into Cellular Responses in Neurons: Ca2+ Signals and Neurotransmitter Release (original) (raw)

Neuronal nicotinic acetylcholine receptors (nAChR) modulate a variety of cellular responses, including Ca 2ϩ signals and neurotransmitter release, which can influence neuronal processes such as synaptic efficacy and neuroprotection. In addition to receptor activation through the agonist binding site, an allosteric modulation of nAChR has also been described for a novel class of allosteric ligands. Of these, the acetylcholinesterase inhibitor and Alzheimer drug galantamine represents the prototypical allosteric ligand, based on its potentiation of nAChRevoked single-channel and whole-cell currents. The aim of this study was to establish whether the allosteric potentiation of nAChR currents is transduced in downstream cellular responses to nAChR activation, namely increases in intracellular Ca 2ϩ and [ 3 H]noradrenaline release. In SH-SY5Y cells, galantamine potentiated nicotine-evoked increases in intracellular Ca 2ϩ and [ 3 H]noradrenaline release with a bell-shaped concentration-response profile; maximum enhancement of nicotine