FEEDING AND GI PEPTIDE EFFECT ON HYPOTHALAMIC/PITUITARY/ADRENAL AXIS

进食和胃肠肽对下丘脑/垂体/肾上腺轴的影响

• 批准号: 6204081
• 负责人: LINDA D SANDER
• 金额: $ 11.77万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204081
• 关键词: bombesin; cholecystokinin; corticotropin releasing factor; gastric inhibitory peptide; gastrin releasing peptide; gastrins; gastrointestinal function; hormone receptor; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory rat; leptin; nutrient intake activity; nutrition related tag; statistics /biometry; stereotaxic techniques; stress; vasoactive intestinal peptide

In humans, dogs and, under appropriate circumstances, rats, the ingestion of food elicits increases in the secretion of the hypothalamic-pituitary- adrenal (HPA) axis. The hormonal and neural pathways linking these events have not been established although they are thought to involve brain-gut peptides such as vasoactive intestinal peptide (VIP), chlocystokinin (CCK), and gastrin releasing peptide (GRP), all of which have been shown to simulate the HPA axis when administered either centrally or peripherally the hypothesis on which the proposed studied are based is that the brain-gut peptides VIP, CCK and/or GRP act either/or both peripherally and centrally to mediate/modulate feeding-induced HPA secretion; that these peptides, acting at multiple receptors, interact with a) each other, b) leptin and c) stress/obesity in such mediation/modulation. In order to test this hypothesis we intend to: Specific Aim 1-establish the brain site(s) at which CCK, bombesin/GRP and VIP mediate/modulate feeding-induced HPA secretion via stereotaxic administration of specific receptor antagonists; Specific Aim 2- further characterize interactions of the multiple receptors for CCK/gastrin, GRP/NMB (neuromedin B) and VIP in regulating feeding-induced HPA secretion; Specific Aim 3-establish the role of leptin in the mediation of peptide (CCK, VIP and bombesin)- and feeding-induced HPA secretion via co- administration of leptin to fasted animals; and Specific Aim 4-examine the influence of brain-gut peptides in modulating HPA secretion during stress induced feeding and anorexia, using tail- pinch and isolation/crowding models of stress. Given the importance of these hormones of the HPA axis in regulating the responses of the body to stress and the apparent regulation of HPA axial function by the timing of food ingestion, an understanding of the mechanisms through which food ingestion alters HPA axial function is critical to our understanding of the body's response to stress.

在人类中，狗和在适当的情况下，摄入食物引起的摄入在下丘脑 - 垂体 - 肾上腺（HPA）轴的分泌中增加。尽管人们认为它们涉及诸如血管活性肠道肽（VIP）（VIP），CHLOCYSTOKININ（CCK）和GASTRIN释放肽（GRP）等脑guut肽，但均未建立与这些事件联系的激素和神经途径，但已显示为了模拟HPA轴时，当中央或外围给予拟议所研究的假设是基于脑甲状肽VIP，CCK和/或GRP ACT的假设是/或外围和中心介导/或中心介导的HPA分泌;这些作用于多种受体的肽相互作用a）彼此相互作用，b）瘦素和c）这种介导/调节中的应激/肥胖症。为了检验这一假设，我们打算：特定的目标1-建立CCK，Bombesin/GRP和VIP介导/调节喂养诱导的HPA分泌的大脑部位，通过特定受体拮抗剂的立体定位给药；具体目标2-进一步表征了CCK/Gastrin，GRP/NMB（Neuromedin b）的多个受体的相互作用和调节喂养引起的HPA分泌方面的VIP；特定的目标3建立瘦素在肽介导（CCK，VIP和BOMBESIN）中的作用 - 以及通过将瘦素共同给药对禁食动物的喂养引起的HPA分泌；和特定的目标4-陈述脑肠肽在压力诱导的喂养和厌食期间调节HPA分泌的影响，使用尾巴和隔离/拥挤的压力模型。鉴于HPA轴这些激素在调节身体对压力的反应以及通过食物摄入时间的明显调节HPA轴向功能的重要性，因此了解食物摄入会改变HPA轴向功能至关重要的机制至关重要的机制至关重要我们对身体对压力的反应的理解。