NPY AND THE PLATELET-VASCULAR INTERACTION

我们实验室最近的研究表明，大鼠血小板 含有并释放具有神经肽Y免疫反应性（NPY- ir），在高效液相色谱（HPLC）中与真正的NPY共沉淀。 我们发现 血小板具有特异性、高亲和力的NPY结合位点， 剂. 这些发现，沿着先前已知的心血管疾病， NPY的作用（血管收缩和血管收缩放大 行动）有重要的影响，在心血管功能， 涉及血小板聚集的病理生理状态，特别是 关于血小板-血管相互作用。NPY，36-氨基酸 肽，以前已知是丰富的大脑，节后， 支配心血管系统的交感去甲肾上腺素能神经，和 肾上腺髓质中含有儿茶酚胺的嗜铬细胞。 是 交感神经刺激期间与去甲肾上腺素（NE）共同释放 以及在动物和人类的长期和强烈的压力下。 因此 至少有两个潜在的来源循环NPY：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)血小板源性神经肽Y在血小板聚集中具有重要作用。 病理生理状态下的血管相互作用。 这项建议会 重点研究血小板源性NPY-ir的鉴定及其生物活性， 血小板中NPY结合和第二信使系统，NPY功能 血小板，并确定是否血小板系统的NPY有助于 心血管[病理生理学]模型中血流动力学紊乱 涉及血小板活化。 这些目标将在 研究人员以前使用的几个实验模型， 关于NPY的研究，包括大鼠和人血小板的体外研究，以及 在体评价血液动力学模型。Npy，如果被同情的 在心血管病理生理事件期间，神经和血小板可能 作为血管-血小板相互作用的重要介质出现， 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.