Department of Clinical and Toxicological Analyses, University of Sao Paulo, Sao Paulo, Brazil.
Curr Top Med Chem. 2021;21(3):171-180. doi: 10.2174/1568026620666200826122716.
The nucleotides were discovered in the early 19th century and a few years later, the role of such molecules in energy metabolism and cell survival was postulated. In 1972, a pioneer work by Burnstock and colleagues suggested that ATP could also work as a neurotransmitter, which was known as the "purinergic hypothesis". The idea of ATP working as a signaling molecule faced initial resistance until the discovery of the receptors for ATP and other nucleotides, called purinergic receptors. Among the purinergic receptors, the P2Y family is of great importance because it comprises of G proteincoupled receptors (GPCRs). GPCRs are widespread among different organisms. These receptors work in the cells' ability to sense the external environment, which involves: to sense a dangerous situation or detect a pheromone through smell; the taste of food that should not be eaten; response to hormones that alter metabolism according to the body's need; or even transform light into an electrical stimulus to generate vision. Advances in understanding the mechanism of action of GPCRs shed light on increasingly promising treatments for diseases that have hitherto remained incurable, or the possibility of abolishing side effects from therapies widely used today.
核苷酸于 19 世纪早期被发现,几年后,人们提出这些分子在能量代谢和细胞存活中的作用。1972 年,Burnstock 及其同事的开创性工作表明,ATP 也可以作为神经递质,这被称为“嘌呤能假说”。ATP 作为信号分子的想法最初受到抵制,直到发现 ATP 和其他核苷酸的受体,称为嘌呤能受体。在嘌呤能受体中,P2Y 家族非常重要,因为它包含 G 蛋白偶联受体(GPCR)。GPCR 在不同生物中广泛存在。这些受体使细胞能够感知外部环境,包括:感知危险情况或通过嗅觉检测信息素;食物的味道,不应该吃;对根据身体需要改变新陈代谢的激素做出反应;甚至将光转化为电刺激以产生视觉。对 GPCR 作用机制的理解的进展为治疗迄今仍无法治愈的疾病提供了越来越有希望的方法,或者有可能消除当今广泛使用的治疗方法的副作用。