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In the present study, the involvement of P2Y<jats:sub>2<\/jats:sub> receptors in the hypertensive effect of nucleotides was investigated by use of antagonists and of a siRNA designed for the P2Y<jats:sub>2<\/jats:sub> receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>Agonists of the P2Y<jats:sub>2<\/jats:sub> receptor a as well as P2 antagonists were applied to eyes of New Zealand rabbits, and the changes in IOP were followed for up to 6\u2003h. Cloning of the P2Y<jats:sub>2<\/jats:sub> receptor cDNA was done using a combination of degenerate reverse transcription PCR (RT\u2010PCR) and rapid amplification of cDNA ends (RACE). siRNA was synthesized and tested by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Single doses of 2\u2010thioUTP, UTP\u2010\u03b3\u2010S and UTP increased IOP. This behaviour was concentration\u2010dependent and partially antagonized by reactive blue 2. Silencing the P2Y<jats:sub>2<\/jats:sub> receptor was observed in the ciliary body by immunohistochemistry labelling, where a reduction in the immunofluorescence was observed. This reduction in the expression of the P2Y<jats:sub>2<\/jats:sub> receptor was concomitant with a reduction in IOP, which was measurable 24\u2003h after treatment with the siRNA, maximal after 2 days, followed by a slow increase towards control values for the following 5 days. Application of the P2Y<jats:sub>2<\/jats:sub> agonists after pretreatment of the animals with this siRNA did not produce any change in IOP.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS AND IMPLICATIONS<\/jats:title><jats:p>P2Y<jats:sub>2<\/jats:sub> receptors increase IOP in New Zealand rabbits. The application of a siRNA for this receptor significantly reduced IOP, suggesting that this technology might be used for the treatment of glaucoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2011.01586.x","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T19:50:29Z","timestamp":1310154629000},"page":"1163-1172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Silencing of P2Y<sub>2<\/sub> receptors reduces intraocular pressure in New Zealand rabbits"],"prefix":"10.1111","volume":"165","author":[{"given":"Alba","family":"Martin\u2010Gil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jes\u00fas Perez","family":"de 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