Adenosine-5'-diphosphate is a natural agonist for the purinergic P2Y receptors, including P2Y1, P2Y12, and P2Y13, and can directly bind to and trigger downstream signaling cascades[1]. Purinergic receptors are a class of membrane molecules present in almost all mammalian tissues and are involved in various cellular functions, including cell proliferation and migration, vascular reactivity, apoptosis, and cytokine secretion[2]. Adenosine-5'-diphosphate is a natural purine nucleotide composed of a pyrophosphate group, ribose, and adenine, and is the main product of ATP dephosphorylation by ATPase and can be rephosphorylated to ATP by ATP synthase[3]. As a downstream metabolite of ATP, Adenosine-5'-diphosphate activates purinergic receptors to participate in multiple cellular processes, such as respiration, biosynthetic reactions, cell movement, cell division, and the proliferation and migration of neural stem cells, and is commonly used to study platelet aggregation, antithrombotic mechanisms, and cellular energy metabolism[4][5].
In vitro, treatment of fibroblast-like synoviocyte (FLS) cells with Adenosine-5'-diphosphate (100µM) for 24h significantly induces monocyte chemotactic protein 1 (MCP-1)/ C–C motif chemokine ligand 2 (CCL2) expression via P2Y13 receptors in an MEK/ERK-dependent manner[6].
In vivo, intravenous Adenosine-5'-diphosphate infusions of 2, 4, 8mg/kg/hour during 3 subsequent 20-minute periods in anesthetized Wistar rats induces systemic and renal vasodilation, leading to a gradual, dose-dependent 15% decrease in mean arterial pressure, a sustained increase in renal blood flow, and a 25% decrease in renal vascular resistance, while renal medullary perfusion remains unaffected[7].
References:
[1] Li Y, Yin C, Liu P, Li D, Lin J. Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y1 Receptor. Sci Rep. 2017;7(1):13764.
[2] Huang Z, Xie N, Illes P, et al. From purines to purinergic signalling: molecular functions and human diseases. Signal Transduct Target Ther. 2021;6(1):162.
[3] Bjelobaba I, Janjic MM, Stojilkovic SS. Purinergic signaling pathways in endocrine system. Auton Neurosci. 2015;191:102-116.
[4] Liu Y, Niu H, Wang C, et al. Bio-inspired, bio-degradable adenosine 5'-diphosphate-modified hyaluronic acid coordinated hydrophobic undecanal-modified chitosan for hemostasis and wound healing. Bioact Mater. 2022;17:162-177.
[5] Jacobson KA, Ivanov AA, de Castro S, Harden TK, Ko H. Development of selective agonists and antagonists of P2Y receptors. Purinergic Signal. 2009;5(1):75-89.
[6] Yokota S, Chosa N, Matsumoto S, Satoh K, Ishisaki A. Extracellular adenosine 5'-diphosphate promotes MCP-1/CCL2 expression via the P2Y13 purinergic receptor/ERK signaling axis in temporomandibular joint-derived mouse fibroblast-like synoviocytes. Mol Biol Rep. 2023;50(2):1595-1602.
[7] Roszkowska-Chojecka MM, Walkowska A, Sadowski J, Dobrowolski L. Clopidogrel Partially Counteracts Adenosine-5'-Diphosphate Effects on Blood Pressure and Renal Hemodynamics and Excretion in Rats. Am J Med Sci. 2018;356(3):287-295.
Adenosine-5'-diphosphate是P2Y1、P2Y12、P2Y13等嘌呤能P2Y受体的天然激动剂，可直接结合并触发下游信号级联[1]。嘌呤能受体是一类存在于几乎所有哺乳动物组织中的质膜分子，可参与多种细胞功能，包括细胞的增殖和迁移、血管反应性、细胞凋亡和细胞因子分泌[2]。Adenosine-5'-diphosphate是由焦磷酸基团、戊糖核糖和腺嘌呤构成的天然嘌呤核苷酸，是ATP酶对ATP去磷酸化的主要产物，也可经ATP合酶重新磷酸化为ATP[3]。作为ATP的下游代谢物，Adenosine-5'-diphosphate通过激活嘌呤能受体参与呼吸、生物合成反应、细胞运动、细胞分裂及神经干细胞增殖、迁移等多种细胞过程，常用于研究血小板聚集、抗血栓机制及细胞能量代谢[4][5]。
体外研究中，用100µM的Adenosine-5'-diphosphate处理成纤维样滑膜细胞（FLS）24小时，可通过P2Y13受体显著诱导单核细胞趋化蛋白1（MCP-1）/C-C基序趋化因子配体2（CCL2）的表达，且该过程依赖于MEK/ERK信号通路[6]。
体内研究中，在麻醉的Wistar大鼠中，通过静脉输注Adenosine-5'-diphosphate（剂量分别为2、4、8mg/kg/hour，持续3个20分钟的周期），可诱导全身和肾脏血管扩张，导致平均动脉压逐渐、剂量依赖性地降低15%，肾血流持续增加，肾血管阻力降低25%，而肾髓质灌注未受影响[7]。