ATP|56-65-5|安捷凯

Background

ATP, as a phosphate-group donor for substrate activation in metabolic reactions, is required for the biosynthesis of the intracellular second messenger cyclic adenosine monophosphate (cAMP) and mediates intercellular communication as a bona fide extracellular messenger^[1]. ATP can promote tumor progression or tumor suppression.^[1].

In vitro, the IC50 value for ATP, α,β-meATP, and β,γ-meATP on these P2X receptors regulating IOP (intraocular pressure) was around 1.0 μM. P2X receptors present in the ciliary body are responsible for reducing IOP. Moreover, 1.0 μM ATP under light conditions causes a reduction in IOP of roughly 50% but when darkness occurs, ATP concentration is decreased to 0.30 μM, this concentration scarcely reducing IOP more than 16%^[2]. There is a obvious increase in ECM (extracellular matrix) accumulation has been found in AF (annulus fibrosus) cells at a lower ATP treatment level (20 μM) compared with NP (nucleus pulposus) cells (100 μM), suugestng that AF cells are more sensitive to extracellular ATP than NP cells^[3].

In vivo test it shown that Wistar rats were treated with 25 mg/kg ATP reduced bevacizumab-induced renal toxicity significantly more effectively than benidipine (4 mg/kg)^[4]. Treatment with 1 and 5 mg/kg ATP intra-arterially (i.a.) close to the bladder in rats, produced rapid, phasic, dose-dependent increases in bladder pressure with micturition immediately after injection^[5].

ATP是代谢反应中底物激活的磷酸基供体，用于生物合成细胞内第二信使环状腺苷酸单磷酸（cAMP），并作为真正的细胞外信使介导细胞间通讯。ATP可以促进肿瘤进展或抑制肿瘤。

在离体实验中，ATP、α,β-meATP和β,γ-meATP对调节眼压的这些P2X受体的IC50值约为1.0微米。睫状体中存在的P2X受体负责降低眼压。此外，在光线条件下，1.0微米的ATP会导致眼压降低大约50％，但当黑暗出现时，ATP浓度降至0.30微米，这种浓度几乎只能使眼压降低16％^[2]。与NP（核心纤维）细胞（100μM）相比，在较低的ATP处理水平（20μM）下发现AF（环纤维）细胞中ECM（细胞外基质）积累明显增加，表明AF细胞对细胞外ATP更敏感^[3]。

实验结果表明，在体内测试中，使用25毫克/千克的ATP治疗Wistar大鼠可以更有效地减轻贝伐单抗引起的肾脏毒性，比苯噻啶（4毫克/千克）更为有效。在大鼠的膀胱附近以1和5毫克/千克的剂量进行动脉内注射（i.a.），会迅速、节律性地增加膀胱压力，并在注射后立即排尿。

参考文献:

[1].?Vultaggio-Poma V, et al. Extracellular ATP: A Feasible Target for Cancer Therapy. Cells. 2020 Nov 17;9(11):2496.

[2].?Pintor J. Light-induced ATP release from the lens. Purinergic Signal. 2018 Dec;14(4):499-504.

[3].?Gonzales S, et al. ATP promotes extracellular matrix biosynthesis of intervertebral disc cells. Cell Tissue Res. 2015 Feb;359(2):635-642.

[4].?Kocaturk H, et al. Effect of adenosine triphosphate, benidipine and their combinations on bevacizumab-induced kidney damage in rats. Adv Clin Exp Med. 2021 Nov;30(11):1175-1183.

[5].?Igawa Y, et al. Functional importance of cholinergic and purinergic neurotransmission for micturition contraction in the normal, unanaesthetized rat. Br J Pharmacol. 1993 Jun;109(2):473-9.

Protocol

Cell experiment [1]:
Cell lines	stem cells from human exfoliated deciduous teeth (SHEDs)
Preparation Method	This study investigated the effects of extracellular ATP at a low (0.1 μM) and high (10 μM) concentration on the stemness and osteogenic differentiation of SHEDs. Cells were cultured in either growth medium or osteogenic medium with or without 0.1-10 μM ATP.
Reaction Conditions	0.1-10 μM ATP;
Applications	In growth medium, both concentrations of ATP increased the mRNA expression of pluripotent and osteogenic markers. In contrast, in osteogenic medium, 0.1 μM ATP enhanced in vitro mineralization, whereas 10 μM ATP inhibited this process.
Animal experiment [2]:
Animal models	rats
Preparation Method	Subcutaneous injection of ATP induces pain-related behavior and hyperalgesia to mechanical and heat stimulation in rats.
Dosage form	100 μM and 1 mM; s.c.
Applications	ATP (100 μM and 1 mM, but not 1 μM) superfused for 5 min before the mechanical stimulation suppressed the mechanical responses of muscle thin fibers irrespective of whether they excited the fiber.
参考文献: [1] Techatharatip O, et al. Biphasic Effect of ATP on In Vitro Mineralization of Dental Pulp Cells. J Cell Biochem. 2018 Jan;119(1):488-498. [2] Matsuda T, et al. ATP decreases mechanical sensitivity of muscle thin-fiber afferents in rats. Neurosci Res. 2015 Aug;97:36-44.

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