Kubota K, Sugaya K, Koizumi Y, Toda M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Brain Res. 1989 Apr 17;485(1):62-6. doi: 10.1016/0006-8993(89)90666-5.
Anthramycin (ATM) which is a product of some streptomyces micro-organisms was shown to antagonize the central effects of cholecystokinin (CCK) such as antinociception and satiety and to displace CCK bound to the slices from the brains of mice. Sulfated octapeptide CCK (CCK8) was administered intracisternally to mice at doses of 1 microgram/mouse for inducing antinociception and 200 ng/mouse for satiety. ATM was administered intraperitoneally to mice at doses such as 0.3 and 0.5 mg/kg. CCK8-induced antinociception and satiety were significantly reversed by ATM in those doses. [125I]CCK8 binding to the brain slices was observed autoradiographically. The autoradiograms from the slices were converted to false color images by using a microcomputer. The radioactivity in the autoradiograms was expressed by color spectra in the false color images. Comparison of the binding of [125I]CCK8 to the brain slices in the presence and the absence of ATM revealed that ATM (10(-6) M) clearly displaced the CCK8 binding in the various regions, especially in the cortex, of the brain. These findings suggest that ATM acts as an potent antagonist of CCK in the central nervous system in mice.
氨茴霉素（ATM）是某些链霉菌微生物的产物，已显示出可拮抗胆囊收缩素（CCK）的中枢效应，如抗伤害感受和饱腹感，并能使与小鼠脑切片结合的CCK解离。将硫酸化八肽CCK（CCK8）以1微克/小鼠的剂量脑池内注射给小鼠以诱导抗伤害感受，以200纳克/小鼠的剂量注射以诱导饱腹感。将ATM以0.3和0.5毫克/千克等剂量腹腔注射给小鼠。在这些剂量下，ATM可显著逆转CCK8诱导的抗伤害感受和饱腹感。通过放射自显影观察[125I]CCK8与脑切片的结合。切片的放射自显影片通过微型计算机转换为假彩色图像。放射自显影片中的放射性通过假彩色图像中的色谱表示。比较在有和没有ATM的情况下[125I]CCK8与脑切片的结合情况，发现ATM（10^(-6) M）能明显使脑的各个区域，尤其是皮质中的CCK8结合解离。这些发现表明，ATM在小鼠中枢神经系统中作为CCK的强效拮抗剂发挥作用。
