8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents
8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents
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DOI：
10.1016/j.ejphar.2004.01.031
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发表时间：
2004-03-08
影响因子：
5
通讯作者：
Bonaventure, P
中科院分区：
文献类型：
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作者：
Hedlund, PB;Kelly, L;Bonaventure, P
使用选择性药物和基因敲除小鼠的研究表明，5-HT 7受体在降钙素诱导的低温中起着重要作用。也有证据支持5-HT 1A受体的参与，尽管主要来自使用8-羟基-2（二正丙基氨基）四氢化萘（8-OH-DPAT）（一种5-HT 1A/7受体激动剂）的研究。在此，我们研究了8-OH-DPAT和5-HT 1A和5-HT 7受体的选择性拮抗剂对大鼠、野生型（5-HT 7 +/+）小鼠和敲除（5-HT 7-/-）小鼠体温的影响。在较低剂量下（0.3-0.6 mg/kg，i. p.），8-OH-DPAT降低5-HT 7 +/+小鼠的体温，但不降低5-HT 7-/-小鼠的体温。在较高剂量（lmg/kg，i. p.）8-OH-DPAT在5-HT 7-/-和5-HT 7 +/+小鼠中均诱导体温降低。将5-HT 1A受体拮抗剂（S）-N-叔丁基-3-（4-（2-甲氧基苯基）哌嗪-1-基）-2-苯基丙酰胺（WAY-100135）（10 mg/kg，i. p.）在大鼠和小鼠中抑制8-OH-DPAT在所有剂量下的作用。在5-HT 7 +/+小鼠中，将选择性5-HT 7受体拮抗剂（R）-3-（2-（2-（4-甲基哌啶-1-基）-乙基）吡咯烷-1-磺酰基）苯酚（SB-269970）（10 mg/kg，i. p.）完全抑制0.3mg/kg 8-OH-DPAT引起的体温降低，但高剂量不能抑制。在大鼠中，SB-269970对0.3 mg/kg 8-OH-DPAT诱导的体温过低抑制率为60%。因此，5-HT 7和5-HT 1A受体都以复杂的方式参与体温调节，其中5-HT 7受体在较低的、可能更生理的浓度下更重要。(C)2004 Elsevier B. V.保留所有权利。
Studies using selective drugs and knockout mice have demonstrated that the 5-HT7 receptor plays an instrumental role in serotonin-induced hypothermia. There is also evidence supporting an involvement of the 5-HT1A receptor, although mainly from studies using 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A/7 receptor agonist. Here we studied the effects of 8-OH-DPAT and selective antagonists for the 5-HT1A and 5-HT7 receptors on body temperature in rats, wild-type (5-HT7+/+) mice and knockout (5-HT7-/-) mice. At lower doses (0.3-0.6 mg/kg, i.p.), 8-OH-DPAT decreased body temperature in 5-HT7+/+ mice but not in 5-HT7-/- mice. At a higher dose (I mg/kg, i.p.) 8-OH-DPAT induced hypothermia in both 5-HT7-/- and 5-HT7+/+ mice. The 5-HT1A receptor antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide (WAY-100135) (10 mg/kg, i.p.) inhibited the effect of 8-OH-DPAT at all doses in rats and mice. In 5-HT7+/+ mice the selective 5-HT7 receptor antagonist (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-l-sulfonyl)phenol (SB-269970) (10 mg/kg, i.p.) fully inhibited the hypothermia induced by 0.3 mg/kg 8-OH-DPAT, but not that of higher doses. In rats, SB-269970 caused a 60% inhibition of the hypothermia induced by 0.3 mg/kg 8-OH-DPAT. Thus, both 5-HT7 and 5-HT1A receptors are involved in a complex manner in thermoregulation, with the 5-HT7 receptor being more important at lower, possibly more physiological, concentrations. (C) 2004 Elsevier B.V. All rights reserved.