Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas (N.S.B.); and Louisiana State University School of Medicine, New Orleans, Louisiana (D.J.L.)
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas (N.S.B.); and Louisiana State University School of Medicine, New Orleans, Louisiana (D.J.L.).
Mol Pharmacol. 2019 Jul;96(1):109-114. doi: 10.1124/mol.118.113910. Epub 2019 May 6.
Discovery of the production of gaseous molecules, such as nitric oxide and hydrogen sulfide, within the human body began a new concept in cellular signaling. Over the past 30 years, these molecules have been investigated and found to have extremely important beneficial effects in numerous chronic diseases. Gaseous signaling molecules that diffuse in three dimensions apparently contradict the selectivity and specificity afforded by normal ligand receptor binding and activation. This new concept has also created hurdles in the development of safe and efficacious drug therapy based on these molecules. Mechanisms involving formation of more stable intermediates and second messengers allow for new strategies for safe and effective delivery of these molecules for human disease. The purpose of this review is to highlight the biologic effects of nitric oxide and hydrogen sulfide, their seemingly indistinguishable effects, and how these molecules can be safely harnessed for drug development and precursors or substrates administered for human consumption through applied physiology.
人体内气态分子(如一氧化氮和硫化氢)的产生被发现,这开创了细胞信号传递的新理念。在过去的 30 年中,这些分子已被广泛研究,并被发现对许多慢性疾病具有极其重要的有益作用。能够在三维空间中扩散的气态信号分子显然与正常配体受体结合和激活所提供的选择性和特异性相矛盾。这一新概念也给基于这些分子的安全有效的药物治疗的发展带来了障碍。涉及形成更稳定的中间体和第二信使的机制允许为这些分子的安全有效传递制定新的策略,以便将其用于人类疾病。本文综述的目的是强调一氧化氮和硫化氢的生物学效应、它们看似不可区分的效应,以及如何通过应用生理学将这些分子安全地用于药物开发以及前体或底物的管理,以用于人类消费。