CARDIOVASCULAR BIOLOGY OF NEUROPEPTIDE Y

神经肽Y(NPY)是一种由36个氨基酸组成的多肽，是 包含在交感神经末梢中，并与 去甲肾上腺素产生血管收缩作用。NPY18-36是一个片段 与NPY相反，NPY产生的血液减少 血压和心输出量。这笔赠款的目的是 三个方面：(1)确定NPY拮抗剂的特征以研究 内源性NPY的生理学；(2)研究NPY在体内的作用 血管内皮细胞释放内皮素及其作用的测定 内皮素在介导NPY心血管作用中的作用； (3)确定NPY18-36是否存在于动物体内。 NPY类似物wi))在三个系统中的一个或多个中被评估：(1) 与牛主动脉内皮细胞(BAEC)结合评估 受体结合的结构要求；(2)刺激 从BAEC释放内皮素以评估体外的内源性活性； 对清醒大鼠血压和心率的影响 血管收缩活性的指标。 将使用被动免疫和/或NPY受体拮抗剂 确定内源性NPY在三个系统中的作用：(1) 电刺激后胰腺血流量的变化 胰腺神经；(2)血压的调节 α-肾上腺素能阻滞；(3)血压调节 在30%的出血后。 内皮素放射免疫分析(RIA)将被用来测量 神经肽Y治疗后BAEC释放内皮素的研究这个 NPY诱导的内皮素释放在介导NPY效应中的作用 将使用被动免疫来评估对血压的影响。 在动物中存在NPY片段NPY18-36将是 通过从血液、脑、心脏和心脏中提取多肽进行评估 用放射免疫法测定小鼠脾组织中NPY18-36的含量。的真实性 将使用高压液体评估内源NPY18-36 凝胶过滤层析。 这项授权将定义拮抗剂和细胞活动，即角色 内皮素，神经肽Y。此外，NPY的存在 具有独特生物学作用的片段NPY18-36将被 下定决心。每个目标都提供了新的重要信息-- 心血管调节的生化研究进展。 NPY的拮抗剂将为研究和治疗提供新的途径 男性的心血管功能障碍。

Neuropeptide Y (NPY) is a 36-amino acid-containing peptide that is contained within synpathetic nerve terminals and co-released with norepinephrine to produce vasoconstriction. NPY18-36 is a fragment of NPY that, in contrast to NPY, produces a decrease of blood pressure and cardiac output. The purpose of this grant is threefold: (1) to characterize an NPY antagonist to study the physiology of endogenous NPY; (2) to study the actions of NPY on endothelial cell release of endothelin and to determine the role of endothelin in mediating the cardiovascular actions of NPY; and (3) to determine if NPY18-36 is present in animals. NPY analogs wi)) be evaluated in one or more of three systems: (1) binding to bovine aorta endothelial cells (BAEC) to assess structural requirements for receptor binding; (2) stimulation of endothelin release from BAEC to assess intrinsic activity in vitro; and (3) effects on blood pressure and heart rate in awake rats as an index of vasoconstrictive activity. Passive immunization and/or an NPY receptor antagonist will be used to determine the role of endogenous NPY in three systems: (1) changes in pancreatic blood flow following electrical stimulation of the pancreatic nerve; (2) regulation of blood pressure following alpha-adrenergic blockade; and (3) regulation of blood pressure following 30% hemorrhage. An endothelin radioimmunoassay (RIA) will be used to measure the release of endothelin from BAEC's following NPY treatment. The role of NPY-induced endothelin release in mediating NPY's effects on blood pressure will be assessed using passive immunization. The presence of the NPY fragment, NPY18-36, in animals will be evaluated by extraction of peptides from blood, brain, heart and spleen and measurement of NPY18-36 by RIA. Authenticity of endogenous NPY18-36 will be assessed by using high pressure liquid and gel filtration chromatography. This grant will define antagonists and cellular actions, i.e., role of endothelin, of NPY. In addition, the presence of an NPY fragment with unique biological actions, NPY18-36, will be determined. Each of these goals provides new and important infor- mation on the biochemistry of cardiovascular regulation. Antagonists of NPY will provide new ways to study and perhaps treat cardiovascular dysfunction in man.