Systemic Administration of the TRPV3 Ion Channel Agonist Carvacrol Induces Hypothermia in Conscious Rodents.
Systemic Administration of the TRPV3 Ion Channel Agonist Carvacrol Induces Hypothermia in Conscious Rodents.
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DOI：
10.1371/journal.pone.0141994
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Marrelli SP
中科院分区：
文献类型：
--
作者：
Feketa VV;Marrelli SP
低温治疗是一种有前途的神经保护新策略。然而，缺乏对意识清醒的患者安全有效的低温诱导方法。目前的研究探索了激动剂香芹酚对瞬时受体电位香草酸 3 (TRPV3) 通道的激活作为一种潜在的低温策略。研究发现香芹酚对小鼠和大鼠进行腹腔和静脉注射后可降低核心温度。然而，安全剂量下的降体温作用不大，而静脉注射较高剂量的香芹酚会导致血压显着下降和严重的毒性。对小鼠低温效应机制的实验表明，它与全身热量产生的减少有关，但与寻冷行为的改变无关。此外，在寒冷的环境温度下，降温效果会消失。我们的研究结果表明，虽然 TRPV3 激动剂会在啮齿类动物中诱导体温过低，但由于其效果欠佳且毒性较高，因此作为一种新的药理学方法在意识清醒的患者中诱导体温过低的潜力可能有限。
Therapeutic hypothermia is a promising new strategy for neuroprotection. However, the methods for safe and effective hypothermia induction in conscious patients are lacking. The current study explored the Transient Receptor Potential Vanilloid 3 (TRPV3) channel activation by the agonist carvacrol as a potential hypothermic strategy. It was found that carvacrol lowers core temperature after intraperitoneal and intravenous administration in mice and rats. However, the hypothermic effect at safe doses was modest, while higher intravenous doses of carvacrol induced a pronounced drop in blood pressure and substantial toxicity. Experiments on the mechanism of the hypothermic effect in mice revealed that it was associated with a decrease in whole-body heat generation, but not with a change in cold-seeking behaviors. In addition, the hypothermic effect was lost at cold ambient temperature. Our findings suggest that although TRPV3 agonism induces hypothermia in rodents, it may have a limited potential as a novel pharmacological method for induction of hypothermia in conscious patients due to suboptimal effectiveness and high toxicity.