Cano Victoria, Ezquerra Laura, Ramos M Pilar, Ruiz-Gayo Mariano
Departamento de Farmacología, Tecnología y Desarrollo Farmacéutico, USP-CEU, Boadilla del Monte, Madrid 28668, Spain.
Br J Pharmacol. 2003 Nov;140(5):964-70. doi: 10.1038/sj.bjp.0705513. Epub 2003 Sep 29.
Activation of the hypothalamic-pituitary-adrenal axis by fasting seems to involve cholecystokinin (CCK) receptors. This work aims to characterize the role of endogenous CCK in the activity of the paraventricular nucleus (PVN) of the hypothalamus during food withdrawal. We investigated, by c-Fos immunohistochemistry, the effect of CCK1 and CCK2 receptor antagonists (SR-27,897 and L-365,260, respectively) on c-Fos levels expression induced by food deprivation. Under our conditions, the number of cells expressing c-Fos was reduced both by SR-27,897 and L-365,260 in food-deprived rats. To investigate the importance of glucose availability, we studied the effect of CCK receptor antagonists on c-Fos synthesis induced by the glucose antimetabolite 2-deoxyglucose. In these animals, only SR-27,897 decreased c-Fos expression in the PVN. Our results indicate that the effect of CCK antagonists is mainly perceptible when glucose availability decreases, and suggest that CCK-ergic inputs could drive the activity of the PVN under fasting/low glucose conditions.
禁食激活下丘脑-垂体-肾上腺轴似乎涉及胆囊收缩素(CCK)受体。这项研究旨在明确内源性CCK在食物剥夺期间下丘脑室旁核(PVN)活动中的作用。我们通过c-Fos免疫组织化学方法,研究了CCK1和CCK2受体拮抗剂(分别为SR-27,897和L-365,260)对食物剥夺诱导的c-Fos水平表达的影响。在我们的实验条件下,食物剥夺大鼠中,SR-27,897和L-365,260均降低了表达c-Fos的细胞数量。为了研究葡萄糖可用性的重要性,我们研究了CCK受体拮抗剂对葡萄糖代谢拮抗剂2-脱氧葡萄糖诱导的c-Fos合成的影响。在这些动物中,只有SR-27,897降低了PVN中c-Fos的表达。我们的结果表明,当葡萄糖可用性降低时,CCK拮抗剂的作用主要可被察觉,这表明CCK能神经输入可能在禁食/低血糖条件下驱动PVN的活动。