Masuo Y, Noguchi J, Morita S, Matsumoto Y
Discovery Research Laboratories I, Takeda Chemical Industries, Ibaraki,Japan.
Brain Res. 1995 Nov 27;700(1-2):219-26. doi: 10.1016/0006-8993(95)00978-y.
We investigated the effects of i.c.v. administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the spontaneous motor activity and reserpine-induced hypothermia in murines. The administration of PACAP (1 or 2 nmol) caused a dose-dependent increase in both spontaneous motor activity and rearing behavior in the rat. The peptide (0.1 or 0.2 nmol) counteracted reserpine-induced hypothermia in a dose-dependent manner in mice. On the other hand, i.c.v. injection of vasoactive intestinal polypeptide, which is structurally similar to PACAP, at a dose similar to that of PACAP (2 nmol in rats, 0.2 nmol n mice) did not show a significant effect on either behavior or body temperature. Therefore, the stimulating effect of PACAP observed here may be mediated by PACAP-specific (type I) receptors. PACAP was more potent and longer-lasting than a known potent stimulating peptide, thyrotropin-releasing hormone, in both stimulating motor activity and counteracting reserpine-induced hypothermia. Results of the present study, in combination with those of previous studies identifying endogenous PACAP in the brain, suggest that PACAP may play a important role in the CNS as a stimulant in regulating motor activity and body temperature.
我们研究了脑室内注射垂体腺苷酸环化酶激活多肽（PACAP）对小鼠自发运动活动及利血平诱导的体温过低的影响。给予PACAP（1或2纳摩尔）可使大鼠的自发运动活动及竖毛行为呈剂量依赖性增加。该多肽（0.1或0.2纳摩尔）能以剂量依赖性方式对抗小鼠利血平诱导的体温过低。另一方面，脑室内注射与PACAP结构相似的血管活性肠肽，剂量与PACAP相同（大鼠为2纳摩尔，小鼠为0.2纳摩尔），对行为或体温均未显示出显著影响。因此，此处观察到的PACAP的刺激作用可能由PACAP特异性（I型）受体介导。在刺激运动活动及对抗利血平诱导的体温过低方面，PACAP比已知的强效刺激肽促甲状腺激素释放激素更有效且作用更持久。本研究结果与先前在脑中鉴定出内源性PACAP的研究结果相结合，表明PACAP可能作为一种刺激物在中枢神经系统中对调节运动活动和体温发挥重要作用。
