Cholecystokinin is a Physiological Regulator of Intermeal Interval

胆囊收缩素是间隔时间的生理调节剂

• 批准号: 8437256
• 负责人: JOSEPH R REEVE
• 金额: $ 25.88万
• 依托单位: BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8437256
• 关键词: Acinar Cell; Affinity; Agonist; Attenuated; Behavioral; Binding; Biochemistry; Biological Assay; Blood; Blood - brain barrier anatomy; Brain; Brain region; Cholecystokinin; Cholecystokinin Receptor; Clinical; Diet; Disease; Dose; Eating; Endocrine; Enteral; Event; Fat-Restricted Diet; Fatty acid glycerol esters; Feeding Patterns; Food; Food Intake Regulation; Foundations; Future; Goals; Hormones; Individual; Infusion procedures; Injection of therapeutic agent; Intake; Intestines; Intravenous; Investigation; Knowledge; Left; Length; Location; Measures; Methods; Molecular; Muscle; Neurons; Obesity; Pattern; Peptides; Peripheral; Physiological; Preparation; Process; Radioactive; Radioimmunoassay; Rattus; Regulation; Research; Research Design; Risk; Role; Route; Satiation; Site; Solid; Structure of jugular vein; Techniques; Technology; Testing; Time; Tissues; Travel; Vagotomy; Work; base; behavior observation; camostate; cholecystokinin 58; cholecystokinin 8; feeding; fight against; hindbrain; immunoreactivity; inhibitor/antagonist; intraperitoneal; paracrine; prevent; public health relevance; receptor; research study; weapons

DESCRIPTION (provided by applicant): The goal of this interdisciplinary proposal is to determine the roles and mechanisms of action of large molecular forms of cholecystokinin (CCK) in prolonging the length of the postprandial intermeal interval (IMI) during normal feeding. We will establish the molecular forms of CCK within intestine and those released by a meal into portal and systemic blood, using state-of-the-art peptidomic technology we have developed. Based on persuasive recent findings, we predict that CCK-58 will be the critical probe. To establish a normal meal pattern, a spontaneously-feeding, undisturbed rat preparation will be utilized. To track sequential meals and intermeal intervals, we will employ a reliable and valid technique of behavioral observation; to permit the microstructural analysis of individual meals, we will also record second-by second intakes of solid food, using automated recording. To establish the physiological status of circulating CCK-58, the exogenous peptide (at physiological levels) and its selective receptor antagonists and agonists will be evaluated. Endogenous CCK will also be released using a specific CCK releaser, camostat and feeding patterns analyzed with and without selective antagonists. Potential central sites of action stimulated by exogenous CCK-58 will also be established by the use of vagotomy, Fos-like immunoreactivity and binding or radioactive CCK forms to central sites. The refined behavioral analyses and peptide biochemistry presented in this proposal will provide a decisive test of the hypothesis at risk: two locations of the CCK1 receptor control total daily food intake: the receptors at vagal afferents that regulate meal size and the receptors in specific regions of the brain that regulate IMI. The results of these investigations should further our understanding of how CCK regulates total daily food intake and demonstrate if CCK-58 could be an effective weapon in our fight against obesity.

描述（由申请人提供）：该跨学科建议的目的是确定大分子形式的胆囊动蛋白（CCK）在延长餐后间间间隔（IMI）的长度方面的作用和机制。我们将使用我们已经开发的最先进的肽组技术来建立肠内CCK的分子形式，并在肠道内建立将CCK的分子形式建立。根据有说服力的最新发现，我们预测CCK-58将是关键探测器。为了建立正常的餐食，将使用自发喂养的，不受干扰的大鼠制剂。为了跟踪顺序餐和间隔间的间隔，我们将采用一种可靠且有效的行为观察技术。为了允许对单个餐食进行微观结构分析，我们还将使用自动记录记录第二次固体食品的摄入量。为了建立循环CCK-58的生理状态，将评估外源肽（在生理水平上）及其选择性受体拮抗剂和激动剂。内源性CCK也将使用特定的CCK释放剂，calostat和以有选择性拮抗剂分析的饲料模式释放。外源CCK-58刺激的潜在中央作用部位也将通过使用迷走神经切开术，FOS样免疫反应性以及与中央部位的结合或放射性CCK形式建立。该提案中提出的精致行为分析和肽生物化学将对处于危险的假设进行决定性测试：CCK1受体控制的两个位置总每日食物摄入量：迷走神经传入的受体，这些受体调节了调节IMI的特定区域的粉状量和受体。这些调查的结果应进一步了解CCK如何调节每日食物的总摄入量，并证明CCK-58是否可以成为我们反对肥胖症的有效武器。