NPY AND THE PLATELET-VASCULAR INTERACTION

我们实验室最近的研究表明，大鼠血小板 含有和释放具有神经肽Y免疫反应性的物质(NPY- IR)，与正品NPY在高效液相中共洗脱。我们发现， 血小板具有特定的、高亲和力的NPY结合位点，并具有外源性 探员们。这些发现，以及之前已知的心血管疾病 NPY(血管收缩和血管收缩药放大)的作用 动作)对心血管功能有重要影响 涉及血小板聚集的病理生理状态，特别是 关于血小板与血管的相互作用。神经肽Y，一种36个氨基酸 多肽，此前已知在大脑中含量丰富，节后， 交感去甲肾上腺素能神经支配心血管系统，以及 肾上腺髓质内含儿茶酚胺的嗜铬细胞。它是 交感神经刺激时去甲肾上腺素(NE)的共同释放 在动物和人类长期和强烈的压力下。因此，在那里 至少有两个潜在的NPY循环来源：交感神经- 肾上腺髓质系统和血小板。我们的总体假设是 血小板是神经肽Y的主要来源和作用部位 (NPY)，而血小板来源的NPY在血小板中具有重要作用。 病理生理状态下的血管相互作用。这项提议将 着重于血小板源性NPY-ir的鉴定和生物活性， 血小板NPY结合系统和第二信使系统及其功能 ，并确定NPY的血小板系统是否对 心血管[病理生理模型]中的血流动力学紊乱 涉及到血小板的激活。这些目标将在#年阐述。 研究人员以前在他们的研究中使用的几个实验模型 NPY的研究，包括大鼠和人血小板的体外研究，以及 活体血流动力学模型。NPY，如果由双方同情的人释放 心血管病理生理事件期间的神经和血小板可能 作为血管-血小板相互作用的重要介质， 在休克、血栓形成、中风和心肌梗死中的潜在作用。

Recent studies in our laboratory have demonstrated that rat platelets contain and release substances with neuropeptide Y-immunoreactivity (NPY- ir), which co-elute with authentic NPY in HPLC. We have discovered that platelets have specific, high-affinity NPY binding sites, and exogenous agents. These findings, along with the previously known cardiovascular actions of NPY (vasoconstriction & amplification of vasoconstrictor actions) have important implications in cardiovascular function during pathophysiological states involving platelet aggregation, and specifically with respect to platelet-vascular interactions. NPY, a 36-amino acid peptide, was previously known to be abundant in the brain, postganglionic, sympathetic noradrenergic nerves innervating the cardiovascular system, and catecholamine-containing chromaffin cells of the adrenal medulla. It is co-released with norepinephrine (NE) during sympathetic nerve stimulation and during prolonged and intense stress in animals and humans. Thus, there are at least two potential sources for circulating NPY: the sympatho- adrenomedullary system and platelets. Our overall hypothesis is that platelets are a major source of, and site of action for, neuropeptide Y (NPY), and that platelets derived NPY has important role in platelet- vascular interactions in pathophysiological states. This proposal will focus on the identification of platelet-derived NPY-ir and bioactivity, binding and second messenger systems of NPY in platelets, function of NPY in platelets, and defining whether platelet systems of NPY contributes to hemodynamic derangements in cardiovascular [pathophysiological models involving platelet activation. These objectives will be addressed in several experimental models previously used by the investigators in their studies on NPY, including in vitro studies of rat and human platelets, and in vivo rate hemodynamic models. Npy, if released by both sympathetic nerves and platelets during cardiovascular pathophysiological events may emerge as an important mediator of vascular-platelet interactions, with potential roles in shock, thrombosis, stroke and myocardial infraction.