DOPAMINE RECEPTOR MODULATION OF CHROMAFFIN CELL FUNCTION

多巴胺受体对嗜铬细胞功能的调节

• 批准号: 3238989
• 负责人: ALLAN S SCHNEIDER
• 金额: $ 13.91万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238989
• 关键词: adrenal glands; adrenal medulla; alpha antiadrenergic agent; autonomic ganglion; bacterial toxins; beta antiadrenergic agent; calcium channel blockers; calcium metabolism; catecholamine inhibitor; chemical binding; cholera toxin; chromaffin cells; dopamine; epinephrine; fluorescence spectrometry; fluorescent dye /probe; gel electrophoresis; guanosine triphosphate; membrane activity; membrane permeability; neurochemistry; neuropharmacology; neurotransmitters; norepinephrine; pheochromocytoma; radiotracer; secretion; stress; tissue /cell culture; tissue /cell preparation

The long term goals of this project are to elucidate the role of peripheral dopamine receptors on adrenal chromaffin cells and the mechanisms by which they alter neurotransmitter release. Although dopamine containing cells (SIF cells) are known to be present in sympathetic ganglia, the site of action and role of dopamine in ganglionic function remains obscure. Adrenal chromaffin cells resemble postganglionic, sympathetic neurons in their synthesis, storage and release of catecholamines. It has recently been reported that dopamine receptor agonists inhibit adrenal catecholamine release. We have obtained preliminary evidence for the presence of D2 dopamine receptors on adrenal chromaffin cells, their interaction with GTP binding proteins, and for their inhibition of calcium channels and catecholamine release. We plan to characterize the dopamine receptors on chromaffin cells by radioligand binding techniques, using 3H-N- methylspiperone, a D2 dopamine receptor antagonist, and 3H-N- propylapomorphine, a D2 receptor agonist. The role of dopamine receptors in adrenal medullary function will be determined by measuring the effects of dopaminergic ligands on calcium translocation, cytosolic calcium levels and catecholamine release. The possible role of GTP-binding proteins in the receptor transduction mechanism will be examined by determining the effects of pertussis toxin and cholera toxin and of guanyl nucleotide derivatives on radioligand binding, calcium movements and catecholamine release. In a general sense it is anticipated that new insights into the function of peripheral dopamine receptors and their mechanisms of modulating neurohormone release will result from this project. The specific role of D2 dopamine receptors in regulating adrenal chromaffin cell calcium movements and catecholamine secretion should be clarified. An improved understanding of the pharmacology and cellular regulation of catecholamine release will be relevant to the management of the adrenal medullary tumor, pheochromocytoma. Since adrenaline release is central to the neurochemistry of the acute stress response, there will also be direct relevance to the associated effects on cardiovascular and pulmonary function and hypertension.

该项目的长期目标是阐明 肾上腺寄生虫细胞上的周围多巴胺受体和 它们改变神经递质释放的机制。 尽管已知含多巴胺的细胞（SIF细胞）是 出现在同情神经节中，行动部位和作用 神经节功能中的多巴胺仍然晦涩。 肾上腺 铬蛋白细胞类似于神经节后的交感神经元 它们的合成，储存和释放的儿茶酚胺。 它有 最近有报道说多巴胺受体激动剂抑制 肾上腺儿茶酚胺释放。 我们已经获得了初步 肾上腺上存在D2多巴胺受体的证据 铬蛋白细胞，它们与GTP结合蛋白的相互作用，以及 为了抑制钙通道和儿茶酚胺 发布。 我们计划表征多巴胺受体 使用3H-N-N-通过放射性结合技术通过铬蛋白细胞 甲基旋转，D2多巴胺受体拮抗剂和3H-N-N- D2受体激动剂的丙型氨基酚。 多巴胺的作用 肾上腺髓质功能中的受体将由 测量多巴胺能配体对钙的影响 易位，胞质钙水平和儿茶酚胺释放。 GTP结合蛋白在受体中的可能作用 通过确定的转导机制将进行检查 百日咳毒素和霍乱毒素和圭烷的影响 核苷酸衍生物在放射性结合，钙运动上 和儿茶酚胺释放。 从一般意义上讲，这是可以预料的 对周围多巴胺功能的新见解 受体及其调节神经运动的机制 发布将由该项目产生。 D2的具体作用 多巴胺受体调节肾上腺染色体细胞钙 运动和儿茶酚胺分泌应澄清。 一个 对药理学和细胞的理解有所提高 儿茶酚胺释放的调节将与 肾上腺髓质肿瘤的治疗，嗜铬细胞瘤。 由于肾上腺素释放是神经化学的核心 急性应力反应，也将与 对心血管和肺功能的相关影响以及 高血压。