Takaki A, Nagai K, Takaki S, Yanaihara N, Nakagawa H
Division of Protein Metabolism, Osaka University, Japan.
Physiol Behav. 1990 Dec;48(6):865-71. doi: 10.1016/0031-9384(90)90241-u.
Glutaryl-CCK-8 (Glt-CCK-8, 16-160 pmol) suppressed food intake dose dependently when injected into the ventromedial hypothalamus (VMH) bilaterally, but not when injected unilaterally. In contrast, CCK-8 (160 and 320 pmol) did not suppress food intake when injected into the VMH bilaterally. When injected intraperitoneally, Glt-CCK-8 significantly decreased food intake at a dose of 320 pmol, though not at a dose of 160 pmol, whereas CCK-8 significantly reduced food intake even at a dose of 160 pmol. Pretreatment with proglumide, an antagonist of CCK-8, counteracted the effect on food intake of CCK-8 injected intraperitoneally, but did not influence that of Glt-CCK-8 injected either into the VMH or intraperitoneally. However, CCK-8 (800 pmol) prevented the satiety action of Glt-CCK-8 when injected into the VMH before the latter. Since a large dose of CCK-8 injected into the VMH was reported to suppress food intake, these findings suggest that, among the receptors for the satiety action of CCK, intracranial receptor has lower affinity for CCK-8 than for Glt-CCK-8 and peripheral receptor has higher affinity for CCK-8 than for Glt-CCK-8. Furthermore, bilateral lesions of the lateral part of the dorsal parabrachial nucleus (LPBD), from which the neurons containing a CCK-8-like substance extend fibers to the VMH, enhanced the satiety action of Glt-CCK-8 injected into the VMH. These results support the idea that these neurons which project to the VMH are involved in the satiety action.
将戊二酰-胆囊收缩素-8（Glt-CCK-8，16 - 160皮摩尔）双侧注射到腹内侧下丘脑（VMH）时，可剂量依赖性地抑制食物摄入，但单侧注射时则无此作用。相比之下，CCK-8（160和320皮摩尔）双侧注射到VMH时并不抑制食物摄入。腹腔注射时，Glt-CCK-8在320皮摩尔剂量时可显著减少食物摄入，而160皮摩尔剂量时则无此作用，而CCK-8即使在160皮摩尔剂量时也能显著减少食物摄入。用CCK-8拮抗剂丙谷胺预处理可抵消腹腔注射CCK-8对食物摄入的影响，但不影响VMH注射或腹腔注射Glt-CCK-8的作用。然而，在Glt-CCK-8注射到VMH之前，先将CCK-8（800皮摩尔）注射到VMH可阻断Glt-CCK-8的饱腹感作用。由于据报道向VMH注射大剂量CCK-8可抑制食物摄入，这些发现表明，在CCK饱腹感作用的受体中，颅内受体对CCK-8的亲和力低于对Glt-CCK-8的亲和力，而外周受体对CCK-8的亲和力高于对Glt-CCK-8的亲和力。此外，背侧臂旁核外侧部（LPBD）的双侧损伤增强了注射到VMH的Glt-CCK-8的饱腹感作用，从LPBD中含有CCK-8样物质的神经元发出纤维投射到VMH。这些结果支持了这样一种观点，即这些投射到VMH的神经元参与了饱腹感作用。
