CARDIOVASCULAR BIOLOGY OF NEUROPEPTIDE Y

神经肽Y（NPY）是一种含有36个氨基酸的肽， 包含在交感神经末梢内，并与 去甲肾上腺素产生血管收缩 NPY 18 -36是一个片段 与NPY相反， 血压和心输出量 该补助金的目的是 三重：（1）表征NPY拮抗剂，以研究 内源性NPY的生理学;（2）研究NPY对 内皮细胞释放内皮素，并确定其作用 内皮素介导NPY的心血管作用; (3)以确定NPY 18 -36是否存在于动物中。 在三个系统中的一个或多个中评估NPY类似物：（1） 结合牛主动脉内皮细胞（BAEC），以评估 受体结合的结构要求;（2）刺激 内皮素从BAEC释放以评估体外固有活性; 对清醒大鼠血压和心率的影响， 血管收缩活动的指数。 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） 电刺激后胰腺血流的变化 （2）调节血压， α-肾上腺素能阻滞;和（3）调节血压 出血30%。 内皮素放射免疫测定法（RIA）将用于测量 NPY治疗后BAEC释放内皮素。 的 NPY诱导内皮素释放在介导NPY效应中的作用 将使用被动免疫来评估对血压的影响。 动物中NPY片段NPY 18 -36的存在将被证实。 通过从血液、脑、心脏和血液中提取肽进行评价。 脾脏和放射免疫测定NPY 18 -36。 真实性 内源性NPY 18 -36将通过使用高压液体来评估 和凝胶过滤色谱法。 该补助金将定义拮抗剂和细胞作用，即，作用 内皮素和神经肽Y。 此外，NPY的存在 具有独特生物学作用的片段，NPY 18 -36， 测定 每个目标都提供了新的重要信息- 心血管调节的生物化学信息。 神经肽Y拮抗剂将提供新的研究方法， 人的心血管功能障碍。

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.