Banki Eszter, Pakai Eszter, Gaszner Balazs, Zsiboras Csaba, Czett Andras, Bhuddi Paras Rahul Parkash, Hashimoto Hitoshi, Toth Gabor, Tamas Andrea, Reglodi Dora, Garami Andras
Department of Anatomy PTE-MTA "Lendulet" PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary.
J Mol Neurosci. 2014 Nov;54(3):543-54. doi: 10.1007/s12031-014-0361-0. Epub 2014 Jul 4.
Administration of the long form (38 amino acids) of pituitary adenylate cyclase-activating polypeptide (PACAP38) into the central nervous system causes hyperthermia, suggesting that PACAP38 plays a role in the regulation of deep body temperature (T b). In this study, we investigated the thermoregulatory role of PACAP38 in details. First, we infused PACAP38 intracerebroventricularly to rats and measured their T b and autonomic thermoeffector responses. We found that central PACAP38 infusion caused dose-dependent hyperthermia, which was brought about by increased thermogenesis and tail skin vasoconstriction. Compared to intracerebroventricular administration, systemic (intravenous) infusion of the same dose of PACAP38 caused significantly smaller hyperthermia, indicating a central site of action. We then investigated the thermoregulatory phenotype of mice lacking the Pacap gene (Pacap (-/-)). Freely moving Pacap (-/-) mice had higher locomotor activity throughout the day and elevated deep T b during the light phase. When the Pacap (-/-) mice were loosely restrained, their metabolic rate and T b were lower compared to their wild-type littermates. We conclude that PACAP38 causes hyperthermia via activation of the autonomic cold-defense thermoeffectors through central targets. Pacap (-/-) mice express hyperkinesis, which is presumably a compensatory mechanism, because under restrained conditions, these mice are hypometabolic and hypothermic compared to controls.
将垂体腺苷酸环化酶激活多肽的长型（38个氨基酸）（PACAP38）注入中枢神经系统会引起体温过高，这表明PACAP38在深部体温（Tb）调节中发挥作用。在本研究中，我们详细研究了PACAP38的体温调节作用。首先，我们向大鼠脑室内注入PACAP38，并测量它们的Tb和自主热效应器反应。我们发现，脑室内注入PACAP38会引起剂量依赖性体温过高，这是由产热增加和尾部皮肤血管收缩引起的。与脑室内给药相比，全身（静脉）注入相同剂量的PACAP38引起的体温过高明显较小，表明其作用部位在中枢。然后，我们研究了缺乏Pacap基因（Pacap (-/-)）的小鼠的体温调节表型。自由活动的Pacap (-/-)小鼠全天的运动活动较高，在光照阶段深部体温升高。当Pacap (-/-)小鼠被轻度束缚时，与它们的野生型同窝小鼠相比，它们的代谢率和体温较低。我们得出结论，PACAP38通过中枢靶点激活自主冷防御热效应器导致体温过高。Pacap (-/-)小鼠表现出运动亢进，这可能是一种补偿机制，因为在受限条件下，与对照组相比，这些小鼠代谢低下且体温过低。
