Sazetidine-A activates and desensitizes native α7 nicotinic acetylcholine receptors

Jack L. Brown, Susan Wonnacott

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The aim of this study was to investigate the ability of sazetidine-A, a novel partial agonist at α4β2 nicotinic acetylcholine receptors (nAChRs), to affect the function of native α7 nAChRs in SH-SY5Y cells and primary cortical cultures. The α7-selective positive allosteric modulator PNU-120596 was used to reveal receptor activation, measured as an increase in intracellular calcium using fluorescent indicators. In the absence of PNU-120596, sazetidine-A elicited mecamylamine-sensitive increases in fluorescence in SH-SY5Y cells (EC50 4.2 μM) but no responses from primary cortical neurons. In the presence on PNU-120596, an additional response to sazetidine-A was observed in SH-SY5Y cells (EC50 0.4 μM) and robust responses were recorded in 14 % of cortical neurons. These PNU-120596-dependent responses were blocked by methyllycaconitine, consistent with the activation of α7 nAChRs. Preincubtion with sazetidine-A concentration-dependently attenuated subsequent responses to the α7-selective agonist PNU-282987 in SH-SY5Y cells (IC50 476 nM) and cortical cultures. These findings support the ability of sazetidine-A to interact with α7 nAChRs, which may contribute to sazetidine-A's actions in complex physiological systems.

Original languageEnglish
Pages (from-to)2047-2054
JournalNeurochemical Research
Volume40
Issue number10
Early online date12 Apr 2014
DOIs
Publication statusPublished - Oct 2014

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