Shine J, Potter E K, Biden T, Selbie L A, Herzog H
Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
J Hypertens Suppl. 1994 Dec;12(10):S41-5.
CONTROL OF CARDIOVASCULAR SYSTEM: Neuropeptide Y has three major activities which are important in the modulation of blood pressure homeostasis. When released from sympathetic neurons innervating the cardiovascular system, this peptide causes direct long-lasting vasoconstriction, inhibits the release of noradrenaline and other neurotransmitters and potentiates the action of noradrenaline and other pressor agents.
At least two major subtypes of neuropeptide Y receptor have been defined by pharmacological criteria, and the major subtype involved in the control of blood pressure (Y1) has been isolated by molecular cloning. Analysis of the cloned DNA sequence has confirmed that the receptor is a member of the G protein-coupled receptor superfamily and when expressed in various cell lines can couple to both the inhibition of adenylate cyclase and the elevation of intracellular calcium. NEUROPEPTIDE Y ANTAGONISTS: A specific neuropeptide Y antagonist has been developed which significantly lowers the dose-dependent neuropeptide Y-induced pressor response in normal rats. The inhibition is specific for the peptide and also selective for the postsynaptic Y1 receptor-mediated vasoconstrictor activity. Administration of this specific and selective inhibitor significantly reduces resting arterial blood pressure, which remains depressed for up to 4 h in normal and spontaneously hypertensive rats.
Inhibition of endogenous neuropeptide Y activity demonstrates that this peptide makes a significant contribution to the control of blood pressure and indicates the therapeutic potential of neuropeptide Y inhibitors as a new class of antihypertensive agent. The molecular cloning of the neuropeptide Y receptor subtype responsible for both the direct vasoconstrictor activity of the peptide and the potentiation of the action of other pressor agents represents an important advance in our understanding of the molecular basis of neuropeptide Y action and will help in the development of selective neuropeptide Y antagonists.
心血管系统的控制：神经肽Y具有三种主要活性，这在血压稳态调节中很重要。当从支配心血管系统的交感神经元释放时，这种肽会引起直接的持久血管收缩，抑制去甲肾上腺素和其他神经递质的释放，并增强去甲肾上腺素和其他升压剂的作用。
通过药理学标准已定义了至少两种主要的神经肽Y受体亚型，并且通过分子克隆分离出了参与血压控制的主要亚型（Y1）。对克隆的DNA序列的分析证实该受体是G蛋白偶联受体超家族的成员，并且当在各种细胞系中表达时可与腺苷酸环化酶的抑制和细胞内钙的升高偶联。
神经肽Y拮抗剂：已开发出一种特异性神经肽Y拮抗剂，它可显著降低正常大鼠中剂量依赖性神经肽Y诱导的升压反应。这种抑制对该肽具有特异性，并且对突触后Y1受体介导的血管收缩活性也具有选择性。给予这种特异性和选择性抑制剂可显著降低静息动脉血压，在正常大鼠和自发性高血压大鼠中，血压可保持降低长达4小时。
抑制内源性神经肽Y活性表明该肽对血压控制有重大贡献，并表明神经肽Y抑制剂作为一类新型抗高血压药物的治疗潜力。负责该肽直接血管收缩活性和增强其他升压剂作用的神经肽Y受体亚型的分子克隆代表了我们对神经肽Y作用分子基础理解的重要进展，并将有助于开发选择性神经肽Y拮抗剂。
