SENSORY FUNCTION OF THE LIVER IN EMESIS

呕吐时肝脏的感觉功能

• 批准号: 6139942
• 负责人: MARK FRIEDMAN
• 金额: $ 1.34万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6139942
• 关键词: afferent nerve; cyclophosphamide; denervation; dosage; emesis; ferrets; liver metabolism; liver pharmacology; neurophysiology; serotonin; afferent nerve; cyclophosphamide; denervation; dosage; emesis; ferrets; liver metabolism; liver pharmacology; neurophysiology; serotonin

Nausea and vomiting compromise the health and quality of life of patients with a variety of diseases, and create an obstacle to compliance with treatments that produce these disturbing side effects. Nausea and vomiting can be triggered by appropriate stimulation of several sites in the body, including the gastrointestinal tract and area postrema in the brainstem. The purpose of this project is to determine whether emetic agents and mediators also act in liver to generate a neural signal that triggers vomiting (emesis). Using the ferret, a standard animal model for studies the emetic reflex, we will: (1) Determine whether cyclophosphamide, which is used in cancer chemotherapy, acts in liver to induce emesis by comparing the effects of hepatic portal and jugular (systemic) infusion of different doses of this drug. (2) Determine whether the emetic mediator, 5-hydroxytryptamine (5HT) acts in liver to induce vomiting by comparing the effects of hepatic portal and jugular infusion of different concentrations of 5HT. (3) Investigate whether vagal sensory neurons transmit a hepatic signal for emesis by severing the nerves between the liver to brain. The results of this work should contribute to our knowledge of the mechanisms of nausea and vomiting, and may lead to the development of better treatments for these conditions.

恶心和呕吐会损害各种疾病的患者的健康和生活质量，并构成符合产生这些令人不安的副作用的治疗的障碍。 恶心和呕吐可以通过适当刺激体内的几个部位，包括胃肠道和脑干中的区域postrema触发。 该项目的目的是确定催吐药和介体是否还会在肝脏中起作用以产生触发呕吐（Emesis）的神经信号。 使用雪貂，一种用于研究催血反射的标准动物模型，我们将：（1）确定在癌症化学疗法中使用的环磷酰胺是否作用于肝脏中，通过比较肝门户和乳房（全身）输注这种药物的肝门portal和爵士（全身）。 （2）确定催眠介质5-羟色胺（5HT）是否在肝脏中作用着通过比较肝门户和颈颈5HT的影响来诱导呕吐。 （3）研究迷走神经的感觉神经元是否通过将肝脏之间的神经切断到大脑之间来传递肝脏信号。 这项工作的结果应有助于我们对恶心和呕吐机制的了解，并可能导致为这些疾病的更好治疗发展。