Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice.

Journal Article (Journal Article)

Nicotine elicits hypothermic responses in rodents. This effect appears to be related to nicotinic receptor desensitization because sazetidine-A, an α4β2 nicotinic receptor desensitizing agent, produces marked hypothermia and potentiates nicotine-induced hypothermia in mice. To determine the specificity of sazetidine-A induced hypothermia to β2 subunit-containing nicotinic receptors, we tested its efficacy in β2 knockout (β2(-/-)) mice. These effects were compared with wildtype (WT) and α7 knockout (α7(-/-)) mice. Confirming our earlier results, sazetidine-A elicited a pronounced and long-lasting hypothermia in WT mice. In comparison, sazetidine-A induced a much attenuated and shorter hypothermic response in β2(-/-) mice. This indicates that the greater proportion of sazetidine-A induced hypothermia is mediated via actions on β2-containing nicotinic receptors, while a smaller component of hypothermia induced by sazetidine-A is mediated by non-β2 receptors. Similar to WT mice, α7(-/-) mice showed the full extent of the sazetidine-A effect, suggesting that the hypothermia produced by sazetidine-A did not depend on actions on α7 nicotinic receptor subtype. Three other novel nicotinic receptor desensitizing agents derived from sazetidine-A, triazetidine-O, VMY-2-95 and YL-1-127 also produced hypothermia in WT and α7(-/-) mice. Furthermore, unlike sazetidine-A, triazetidine-O and YL-1-127 did not show any hint of a hypothermic effect in β2(-/-) mice. VMY-2-95 like sazetidine-A did show a residual hypothermic effect in the β2(-/-) mice. These studies show that the hypothermic effects of sazetidine-A and the related compound VMY-2-95 are mainly mediated by nicotinic receptors containing β2 subunit, but that a small component of the effect is apparently mediated by non-β2 containing receptors.

Full Text

Duke Authors

Cited Authors

  • Levin, ED; Sexton, HG; Gordon, K; Gordon, CJ; Xiao, Y; Kellar, KJ; Yenugonda, VM; Liu, Y; White, MP; Paige, M; Brown, ML; Rezvani, AH

Published Date

  • October 15, 2013

Published In

Volume / Issue

  • 718 / 1-3

Start / End Page

  • 167 - 172

PubMed ID

  • 24036108

Pubmed Central ID

  • PMC3844546

Electronic International Standard Serial Number (EISSN)

  • 1879-0712

Digital Object Identifier (DOI)

  • 10.1016/j.ejphar.2013.08.037


  • eng

Conference Location

  • Netherlands