ATPγS tetralithium salt is an analogue of ATP, acting as a potent agonist of G protein-coupled P2Y₂ and P2Y₁₁ receptors (pEC50 = 5.52 for P2Y₁₁) [1].?

The P2Y receptors consist of 8 human subtypes, i.e. P2Y₁, P2Y₂, P2Y₄, P2Y₆, P2Y₁₁, P2Y₁₂, P2Y₁₃, and P2Y₁₄, coupled to G protein-dependent and -independent signaling pathways, including ion channels. The P2Y receptors are involved in controlling levels of extracellular nucleotides and nucleosides, and intracellular signaling pathways [1].?

In PC 12 cells, preincubation of the cells with norepinephrine (NE) and ATPγS tetralithium salt (1 μM) resulted in a persistent increase in uptake of NE, whilst similar pretreatment with ATP did not show this increase. In the presence of ATP, the activation effect produced by ATPγS tetralithium salt on NE uptake was blocked [2]. In TEA3A1 cells, ATPγS tetralithium salt (0 ~ 200 μM) increased Ca²⁺ influx in a dose-dependent manner, with ED50 value of about 50 μM. A maximum level of Ca²⁺ influx was observed when cells were treated with ATPγS tetralithium salt at concentrations above 100 μM. Similar dose-dependent increases in the production of prostaglandin E₂ (PGE₂) were also observed after ATPγS tetralithium salt treatment [3].?

References:

[1]. Jacobson K A, Ivanov A A, de Castro S, et al. Development of selective agonists and antagonists of P2Y receptors. Purinergic Signal, 2009, 5(1): 75-89.

[2]. Hardwick J C, Ehrlich Y H, Hendley E D. Extracellular ATP stimulates norepinephrine uptake in PC12 cells. Journal of Neurochemistry, 1989, 53(5):1512-1518.

[3]. Liu P, Lalor D, Bowser S S, et al. Regulation of arachidonic acid release and prostaglandin E2 production in thymic epithelial cells by ATPgammaS and transforming growth factor-alpha. Cellular immunology, 1998, 188(2): 81-88.