ATP releases ATP or other nucleotides from human peripheral blood leukocytes through purinergic P2 receptors

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• 作者：Marlon De Ita^a ; Mario H. Vargas^b ; ¹ ; Ver&oacute ; nica Carbajal^b ; Blanca Ortiz-Quintero^c ; Cintya L&oacute ; pez-L&oacute ; pez^d ; Marcela Miranda-Morales^e ; Carlos Barajas-L&oacute ; pez^d ; Luis M. Monta&ntilde ; o^a ; ¹ ; ^{lmmr@unam.mx" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Human leukocytes ; ATP/nucleotides ; P2Y receptors ; P2X receptors
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：145
• 期：Complete
• 页码：85-92
• 全文大小：923 K

文摘

Almost every eukaryotic cell releases ATP under certain conditions. The idea that ATP induces the release of ATP has been scantly investigated.

Methods

We explored this possibility by assessing the rate of exogenous ATP breakdown (measured by phosphates production) by human peripheral blood leukocytes. The role of P2Y and P2X receptors was evaluated pharmacologically, by patch clamp, or by flow cytometry.

Key findings

In mononuclear and/or polymorphonuclear cells, ATP increased phosphates formation in a time- and concentration-dependent manner. Uncoupling of P2Y receptors with N-ethylmaleimide and antagonism of P2Y and P2X receptors through suramin reduced phosphate formation after 500 μM ATP, suggesting that part of the phosphate production was due to activation of P2 receptors, with subsequent release of ATP or other nucleotides. Similar results were obtained with UTP and ATPγS. Gadolinium (connexins inhibitor) also significantly reduced the ATP-induced phosphate production. Blockade of P2X receptors with SKF 96365 or NF023 did not modify the phosphate production. In monocytes, 500 μM ATP induced inward currents suggestive of P2X₁ activation, but higher concentrations (1–5 mM) induced inward currents suggestive of P2X₇ activation. We discarded a role of adenosine in the ATP-evoked nucleotides release. Flow cytometry identified that almost all mononuclear and polymorphonuclear cells expressed P2Y_1,2,4,6,11 receptors.

Significance

500 μM ATP induced the release of ATP or other nucleotides through activation of P2Y_2,4,6,11 receptors in human leukocytes, and probably via P2X receptors at higher concentrations. This ATP-induced nucleotides release constitutes a potential mechanism leading to amplification of ATP signaling.