The α7 nicotinic acetylcholine receptor positive allosteric modulator attenuates lipopolysaccharide-induced activation of hippocampal IκB and CD11b gene expression in mice.

Abstract

We have reported that 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) reduces lipopolysaccharide (LPS)-induced hyperalgesia and allodynia in mice. The objective of the present study was to determine the effects of TQS on LPS-induced activation of hippocampal inhibitor of κB (IκB) and cluster of differentiation 11b (CD11b) gene expression involving hyperalgesia and allodynia in mice. We also examined the effects of TQS on microglial phenotype following LPS administration. Pretreatment of TQS (4 mg/kg) reduced the expressions of IκB and CD11b mRNA. Pretreatment of methyllycaconitine (3 mg/kg), an α7 nAChR antagonist, reversed TQS-induced decrease in IκB and CD11b mRNA expressions in the hippocampus indicating the involvement of α7 nAChR. In addition, TQS (4 mg/kg) reversed the LPS-induced microglial morphological changes. These results suggest that TQS reduces LPS-induced IκB and CD11b gene expression and microglial activation associated with hyperalgesia and allodynia by targeting microglial α7 nAChR in the hippocampus.

• Authors: Muzaffar Abbas, Sami Alzarea, Roger L Papke, Shafiqur Rahman
• Journal: Drug discoveries & therapeutics (Drug Discov Ther) 2017 Vol. 11 Issue 4 Pg. 206-211 ISSN: 1881-7831 [Print] Japan
• PMID: 28867753 (Publication Type: Journal Article)

Chemical References

• 4-naphthalene-1-yl-3a,4,5,9b-tetrahydro-3-H-cyclopenta(c)quinoline-8-sulfonic acid amide
• CD11b Antigen
• Chrna7 protein, mouse
• I-kappa B Proteins
• Lipopolysaccharides
• Naphthalenes
• Nicotinic Antagonists
• Quinolines
• RNA, Messenger
• Sulfonamides
• alpha7 Nicotinic Acetylcholine Receptor
• methyllycaconitine
• Aconitine

Topics

• Aconitine (analogs & derivatives, pharmacology)
• Allosteric Regulation
• Animals
• CD11b Antigen (drug effects, genetics)
• Gene Expression (drug effects)
• Hippocampus (drug effects, metabolism)
• I-kappa B Proteins (drug effects, genetics)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Microglia (drug effects, pathology)
• Naphthalenes (pharmacology)
• Nicotinic Antagonists (pharmacology)
• Quinolines (pharmacology)
• RNA, Messenger (drug effects, metabolism)
• Sulfonamides (pharmacology)
• alpha7 Nicotinic Acetylcholine Receptor (antagonists & inhibitors, drug effects)