PNU ‐120596, a positive allosteric modulator of mammalian α7 nicotinic acetylcholine receptor, is a negative modulator of ligand‐gated chloride‐selective channels of the gastropod Lymnaea stagnalis

Our aim was probing the effects of PNU ‐120596, a positive allosteric modulator (PAM) of α7 nicotinic acetylcholine receptors (nAChR), on the anion‐conducting channels. Experiments were performed onLymnaea stagnalis and rat Purkinje neurons and mammalian receptors expressed inXenopus oocytes or PC12 cells. InLymnaea neurons, PNU ‐120596, contrary to α7 nAChR, inhibited chloride currents mediated by two nAChR subtypes, GABA and glutamate receptors; one nAChR subtype demonstrated a strong acceleration of desensitization. With the mammalian glycine and GABAA receptors, PNU ‐120596 was a weak PAM. Thus, our results provide new information about the dependence of PAM action on the receptor structure. AbstractExcitatory α7 neuronal nicotinic receptors (nAChR) are widely expressed in the central and peripheral nervous and immune systems and are important for learning, memory, and immune response regulation. Specific α7 nAChR ligands, including positive allosteric modulators are promising to treat cognitive disorde rs, inflammatory processes, and pain. One of them, PNU‐120596, highly increased the neuron response to α7 agonists and retarded desensitization, showing selectivity for α7 as compared to heteromeric nAChRs, but was not examined at the inhibitory ligand‐gated channels. We studied PNU‐120596 a ction on anion‐conducting channels using voltage‐clamp techniques: it slightly potentiated the response of human glycine receptors expressed in PC12 cells, of r...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research