Sazetidine-A Activates and Desensitizes Native α7 Nicotinic Acetylcholine Receptors

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.

• Publication year

  2014

• Venue

  Neurochemical Research

• Publication date

  2014-04-12

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1007/s11064-014-1302-6PMID 24728867PMCID 4630245
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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