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Regulation of endocrine system is very complex and <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> and its degradable products <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content> and adenosine contribute to its regulation acting as extracellular messengers for purinergic receptors. These include <jats:styled-content style=\"fixed-case\">P2X<\/jats:styled-content> receptors, a family of ligand\u2010gated ion channels whose expression and roles in endocrine tissues are reviewed here. There are seven mammalian purinergic receptor subunits, denoted <jats:styled-content style=\"fixed-case\">P2X1<\/jats:styled-content> through <jats:styled-content style=\"fixed-case\">P2X7<\/jats:styled-content>, and the majority of these subunits are also expressed in secretory and non\u2010secretory cells of endocrine system. Functional channels have been identified in the neuroendocrine hypothalamus, the posterior and anterior pituitary, the thyroid gland, the adrenals, the endocrine pancreas, the gonads, and the placenta. Native channels are capable of promoting calcium influx through its pore in both excitable and non\u2010excitable cells, as well as of increasing electrical activity in excitable cells by membrane depolarization. This leads to generation of calcium transients and stimulation of hormone release. The pattern of expression and action of <jats:styled-content style=\"fixed-case\">P2XRs<\/jats:styled-content> in endocrine system suggest that locally produced <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> amplifies and synchronizes the secretory responses of individual cells. <jats:italic>WIREs Membr Transp Signal<\/jats:italic> 2013, 2:173\u2013180. doi: 10.1002\/wmts.89<\/jats:p><jats:p>Conflict of interest: The authors have declared no conflicts of interest for this article.<\/jats:p><jats:p>For further resources related to this article, please visit the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/wires.wiley.com\/remdoi.cgi?doi=10.1002\/wmts.89\">WIREs 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