NEUROHYPOPHYSIAL POLYPEPTIDES AND RENAL PROSTAGLANDINS

神经垂体多肽和肾前列腺素

• 批准号: 3152546
• 负责人: W Y CHAN
• 金额: $ 11.17万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152546
• 关键词: angiotensin II; antihypertensive agents; arginine vasopressin; bradykinin; diuretics; eicosanoid metabolism; fatty acid biosynthesis; kidney metabolism; oxytocin; prostaglandins; radioimmunoassay; saluretic; thin layer chromatography; vasoconstrictors

Arginine-vasopressin (AVP) and other vasoactive peptides such as angiotensin II and bradykinin stimulate renal prostaglandins (PGs) synthesis. There is evidence that renal PGs serve as negative feedback modulators opposing the hormone-induced antidiuresis and vasoconstriction. It is not known whether the PG-stimulating effect of AVP is related to its antidiuretic or vasopressor activity. We have shown that certain analogs of vasopressin and oxytocin which are devoid of antidiuretic and vasopressor activities stimulate renal excretion of sodium and water. It is possible that the natriuretic-diuretic action of these peptides is mediated via renal PG release. Neurohypophysial peptides may, therefore, have PG-stimulating activity, independent of their antidiuretic or vasopressor activity. We will investigate the PG-stimulating activity of these peptides in rats and examine its relationship to the pressor, antidiuretic and natriuretic activities of the molecule. We will also study the effects of these peptides on the phospholipase activity in renal slices and on the renal microsomal cyclooxygenase activity with the aim to define their site and mechanism of action. Radiochemical methods and radioimmunoassays (RIAs) will be employed for the determination of PGs. Our long-term goal is to produce specific renal PG-releasing peptides. Renal PGs modulate renal circulation and may also function as a physiologic antihypertensive mechanism. Specific renal PG-releasing peptides may represent a novel class of drugs that may have potential for the treatment of renovascular and hypertensive diseases.

精氨酸加压素 (AVP) 和其他血管活性肽，例如 血管紧张素 II 和缓激肽刺激肾脏前列腺素 (PG) 合成。 有证据表明肾脏 PG 起到负反馈作用 对抗激素诱导的抗利尿和血管收缩的调节剂。 目前尚不清楚 AVP 的 PG 刺激作用是否与其 抗利尿或血管加压活性。 我们已经证明某些类似物 加压素和催产素，不含抗利尿剂和 血管加压活性刺激肾脏排泄钠和水。 它 这些肽的利钠利尿作用可能是 通过肾 PG 释放介导。 因此，神经垂体肽可能， 具有 PG 刺激活性，与其抗利尿剂或药物无关 血管加压活性。 我们将研究 PG 刺激活性 大鼠体内的这些肽并检查其与升压源的关系， 该分子的抗利尿和利钠尿活性。 我们也会 研究这些肽对肾磷脂酶活性的影响 切片和肾微粒体环氧合酶活性，目的是 定义它们的位点和作用机制。 放射化学方法和 将采用放射免疫测定法 (RIA) 来测定 PG。 我们的长期目标是生产特定的肾脏 PG 释放肽。 肾 PG 调节肾循环，也可作为生理调节剂。 抗高血压机制。 特定的肾 PG 释放肽可能 代表一类可能具有治疗潜力的新型药物 肾血管和高血压疾病。