Cano Victoria, Ezquerra Laura, Ramos M Pilar, Ruiz-Gayo Mariano
Departamento de Farmacología, Tecnología y Desarrollo Farmacéutico, Universidad San Pablo-CEU, Urbanización Montepríncipe, Boadilla del Monte, Madrid 28668, Spain.
Br J Pharmacol. 2003 Oct;140(4):647-52. doi: 10.1038/sj.bjp.0705477.
Cholecystokinin (CCK) is a postprandial hormone that elicits a satiating effect and regulates feeding behaviour. CCK has been shown to enhance the effect of leptin in several experimental paradigms. The goal of this work was to characterize the effect of endogenous CCK on plasma leptin content by using CCK receptor antagonists. Therefore, we administered SR-27897, a selective CCK1 receptor antagonist, and L-365260, a selective CCK2 receptor antagonist, to fed and food-deprived rats and determined plasma leptin concentration by enzyme immunoassay. Plasma insulin and glucose concentration as well as food intake were also determined. Under our conditions, SR-27897 increased plasma concentration of leptin both in fed and food-deprived rats. It also increased food intake as well as plasma concentration of insulin in fed animals. L-365260 increased plasma leptin concentration only in fed rats. In animals receiving exogenous leptin, CCK-8 increased the ratio between the concentration of leptin in cerebrospinal fluid and plasma. These results show that CCK receptor antagonists increases plasma concentration of leptin and suggest that endogenous CCK may facilitate the uptake of plasma leptin to the cerebrospinal fluid.
胆囊收缩素（CCK）是一种餐后激素，可产生饱腹感并调节进食行为。在多个实验范式中，CCK已被证明能增强瘦素的作用。这项研究的目的是通过使用CCK受体拮抗剂来表征内源性CCK对血浆瘦素含量的影响。因此，我们给喂食的和禁食的大鼠注射了选择性CCK1受体拮抗剂SR - 27897和选择性CCK2受体拮抗剂L - 365260，并通过酶免疫测定法测定血浆瘦素浓度。还测定了血浆胰岛素和葡萄糖浓度以及食物摄入量。在我们的实验条件下，SR - 27897在喂食的和禁食的大鼠中均提高了血浆瘦素浓度。它还增加了喂食动物的食物摄入量以及血浆胰岛素浓度。L - 365260仅在喂食的大鼠中提高了血浆瘦素浓度。在接受外源性瘦素的动物中，CCK - 8增加了脑脊液中瘦素浓度与血浆中瘦素浓度的比值。这些结果表明，CCK受体拮抗剂可提高血浆瘦素浓度，并提示内源性CCK可能促进血浆瘦素向脑脊液的摄取。
