Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice.
Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice.
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DOI：
10.1016/j.ejphar.2013.08.037
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发表时间：
2013-10-15
影响因子：
5
通讯作者：
Rezvani, Amir H.
中科院分区：
文献类型：
--
作者：
Levin, Edward D.;Sexton, Hannah G.;Gordon, Karen;Gordon, Christopher J.;Xiao, Yingxian;Kellar, Kenneth J.;Yenugonda, Venkata Mahidhar;Liu, Yong;White, Michael P.;Paige, Mikell;Brown, Milton L.;Rezvani, Amir H.
尼古丁诱发啮齿类动物的低温反应。这种效应似乎与烟碱受体脱敏有关，因为沙泽替丁-A（一种α4β2烟碱受体脱敏剂）可在小鼠中产生显著的体温降低并增强烟碱诱导的体温降低。为了确定沙泽替丁-A诱导的低温对含β2亚基的烟碱受体的特异性，我们在β2敲除（β2−/−）小鼠中测试了其功效。这些效应与野生型（WT）和α7敲除（α7−/−）小鼠进行了比较。与我们早期的结果一致，沙泽替丁-A在WT小鼠中引起明显且持久的体温过低。相比之下，sazetidine-A在β2−/−小鼠中诱导了更弱和更短的低温反应。这表明，大部分沙泽替丁-A诱导的体温降低是通过对含β2烟碱受体的作用介导的，而沙泽替丁-A诱导的体温降低的较小组分是由非β2烟碱受体介导的。与野生型小鼠相似，α7−/−小鼠表现出沙泽替丁-A的全部效应，表明沙泽替丁-A产生的体温降低不依赖于对α7烟碱受体亚型的作用。其他三种新的烟碱受体脱敏剂，分别来自于sazetidine-A、triazetidine-O、VMY-2-95和YL-1-127，它们在WT和α7−/−小鼠中也产生了低体温。此外，与sazetidine-A不同，triazetidine-O和YL-1-127在β2−/−小鼠中没有显示出任何降低体温的作用。VMY-2-95与沙泽替丁-A一样，在β2−/−小鼠中确实显示出残留的低温效应。这些研究表明，sazetidine-A及其相关化合物VMY-2-95的降温作用主要由含β_2亚单位的烟碱受体介导，但也有一小部分由非β_2亚单位的受体介导。
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 nicotinic 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.
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DOI：
10.1124/jpet.108.145292
发表时间：
2009-02-01
影响因子：
3.5
作者：
Buccafusco, Jerry J.;Beach, J. Warren;Terry, Alvin V., Jr.
通讯作者：
Terry, Alvin V., Jr.
影响因子：
3.6
作者：
MARKS, MJ;MINER, L;COLLINS, AC
通讯作者：
COLLINS, AC
影响因子：
4.7
作者：
Ruskin, David N.;Anand, Rene;LaHoste, Gerald J.
通讯作者：
LaHoste, Gerald J.
DOI：
10.1124/jpet.109.162073
发表时间：
2010-03-01
影响因子：
3.5
作者：
Levin, Edward D.;Rezvani, Amir H.;Kellar, Kenneth J.
通讯作者：
Kellar, Kenneth J.
影响因子：
3.6
作者：
Xiao, Yingxian;Fan, Hong;Kellar, Kenneth J.
通讯作者：
Kellar, Kenneth J.