STUDY OF ROLES OF TACHYKININS IN THE NERVOUS SYSTEM

P物质(SP)在某些系统中被显示为调节这些活动 乙酰胆碱和去甲肾上腺素。虽然调制的效果 经典神经递质可能是P物质的重要功能之一。 神经系统，它完成这一任务的机制是未知的。服务提供商 是速激宁家族中第一个被发现的成员 大脑。最近两种新的速激肽，神经激肽A(NKA)和神经激肽B (NKB)，在哺乳动物神经组织中发现。详细解剖 NKA和NKB的分布及其结合位点尚不清楚。它 也不知道NKA和NKB是否有自己的调节作用。 将在兔体内制备抗NKA和NKB的多克隆抗血清。 它们在大鼠脑内的分布将通过两种显微解剖方法进行研究。 结合放射免疫分析和免疫组织化学方法。我们会 确定人脑中是否存在NKA和NKB，如果存在， 地区。因为在帕金森氏症、亨廷顿氏症和 阿尔茨海默病，我们将确定NKA和NKB的水平是否 在这些疾病中也发生了变化。NKA和NKB在大鼠体内的结合部位 大脑将通过膜和切片结合技术和 通过放射自显影定位。 培养的大鼠星形胶质细胞中SP增强去甲肾上腺素对cAMP的刺激作用 在不刺激营地生产本身的情况下形成。培养的星形胶质细胞 将作为一个系统来发展，系统地研究 速激肽调节β肾上腺素能刺激cAMP升高。 将进行完整细胞和膜的结合研究。 评价速激肽对β-受体亲和力和数量的影响 肾上腺素能受体。速激肽对血管活性的影响 腺苷环化酶、磷酸二酯酶和磷脂酰肌醇代谢 也有待研究。我们对星形胶质细胞的发现将应用于大脑 速激肽或其结合部位显著水平的区域 对速激肽作用的生化机制进行了研究 大脑。 速激肽家族中的一个成员SP被认为扮演着一个 在锥体外系和伤害性感受系统中起重要作用。服务提供商拥有 在某些退行性神经疾病中也显示出减少 疾病。拟议中的研究将阐明大脑中的区域 哪些速激肽与神经功能和功能障碍有关 它们所依据的生化机制。

Substance P (SP) has been shown in certain systems to modulate the actions of acetylcholine and norepinephrine. Although modulation of the effects of classic neurotransmitters may be one of the important functions of SP in the nervous system, the mechanisms by which it does this are unknown. SP was the first member of the tachykinin family to be identified in the brain. Recently two new tachykinins, neurokinin A (NKA) and neurkinin B (NKB), were identified in mammalian nervous tissue. Detailed anatomical distributions of NKA and NKB and their binding sites remains unknown. It is also not known whether NKA and NKB have modulatory actions of their own. Polyclonal antisera will be raised in rabbits against NKA and NKB, and their distributions in rat brain will be studied by both microdissection combined with radioimmunoassay and by immunshistochemistry. We will determine if NKA and NKB ae present in human brain and, if so, in which regions. Because SP is reduced in Parkinson's, Huntington's, and Alzheimer's diseases, we will determine whether levels of NKA and NKB are also changed in these diseases. The binding sites for NKA and NKB in rat brain will be characterized by membrane and slice binding techniques and localized by autoradiography. In cultured rat astrocytes SP augments norepinephrine's stimulation of cAMP formation without stimulating cAMP production itself. Cultured astrocytes will be developed as a system to systematically study mechanisms of tachykinin modulation of beta adrenergic stimulated increase in cAMP. Binding studies both in intact cells and with membranes will be performed to assess the effects of tachykinins on the affinity and number of beta adrenergic receptors. The effect of tachykinins on the activity of adenylate cyclase, phosphodiesterase, and phosphoinositide metabolism will also be studied. Our findings from astrocytes will be applied to brain regions in which significant levels of tachykinins or their binding sites are found to study the biochemical mechanism of tachykinin action in the brain. One member of the tachykinin family, SP, is acknowledged to play a significant role in the extrapyramidal and nociceptive systems. SP has also been shown to be decreased in certain degenerative neurological diseases. The proposed studies will elucidate regions of the brain in which tachykinins are involved in neurological function and dysfunction and biochemical mechanisms by which they act.