SOMATOSTATIN: ROLE IN STRESS INDUCED EPINEPHRINE RELEASE

目前的证据支持生长抑素相关多肽的假设 包含在中枢神经系统(CNS)中，参与 肾上腺髓质肾上腺素分泌的调节。建议在 这项拨款申请是必要的研究，以严格检验这一点。 假设。 生长抑素-28(SS-28)将被显微注射到不同的大脑中 清醒大鼠脑实质确定中枢神经系统的作用部位 这种多肽能抑制肾上腺肾上腺素的分泌。曾经是一个遗址(S) 生长抑素受体拮抗剂SS-28的作用 将显微注射到这个部位以确定阻断的效果 内源性生长抑素对肾上腺肾上腺素分泌的影响 含生长抑素的神经纤维和细胞的中枢神经解剖 身体及其与SS-28中枢神经系统作用地点的关系将是 用免疫组织化学和逆行运输相结合的方法 方法：研究方法。对含Aomatostatin胞体定位的认识 投射到SS-28的作用地点将为 这些细胞体或它们的部分被耗尽的实验 多肽或销毁。这些实验，除了生长抑素 拮抗剂实验，将提供有关生理学的信息 内源性生长抑素相关肽在血管紧张素转换酶调控中的重要作用 肾上腺髓质。将寻求对这一假设的进一步支持 研究生长抑素在脑内被确认为 在调节肾上腺肾上腺素分泌方面很重要。生理学 研究肾上腺肾上腺素分泌的模型包括 胰岛素诱导的低血糖、冷暴露、运动、血糖 全血给药和扩容。

Current evidence supports the hypothesis that somatostatin-related peptides contained within the central nervous system (CNS) participate in the regulation of epinephrine secretion from the adrenal medulla. Proposed in this grant application are the studies necessary to critically test this hypothesis. Somatostatin-28 (SS-28) will be microinjected into different brain parenchymal regions of awake rats to determine the CNS site of action of this peptide to inhibit adrenal epinephrine secretion. Once a site(s) of action of SS-28 has been characterized a somatostatin-receptor antagonist will be microinjected into this site to determine the effects of blocking the actions of endogenous somatostatins on adrenal epinephrine secretion. The CNS neuroanatomy of somatostatin-containing nerve fibers and cell bodies and their relationship to the CNS site of action of SS-28 will be assessed using combined immunohistochemical and retrograde transport methods. Knowledge of the location of aomatostatin-containing cell bodies projecting to the site of action of SS-28 will provide the basis for experiments in which these cell bodies or their porjections are depleted of peptide or destroyed. These experiments, in addition to the somatostatin antagonist experiments, will provide information on the physiologic importance of endogenous somatostatin related peptides in the regulation of the adrenal medulla. Further support for this hypothesis will be sought by investigating somatostatin turnover in brain areas identified to be important in the regulation of adrenal epinephrine secretions. Physiologic models for the study of adrenal epinephrine secretion will include insulin-induced hypoglycemis, cold exposure, exercise, glucose administration and volume expansion by administration of whole blood.