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J.J. Pintor, T. Pelaez, A. Peral; Regulation of Intraocular Pressure by Adenosine 5'tetraphosphate, Ap4 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4386.
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Purpose: To investigate the presence and physiological effect of adenosine 5'tetraphosphate (Ap4) in the rabbit aqueous humour Methods: New Zealand rabbits were anaesthetised with propofol (1.5 mg/Kg) and the aqueous humour was pulled out with a 30 G sringe by the sclero-corneal limbus. Nucleotide analysis was performed by ion pair HPLC and ultravioled detection. IOP measurments were carried out by means of a TONOPEN. Different doses (10-2 M to 10-10 M) were topically applied to display a concentration-response curve. For the antagonists, single doses of 100 µM were pre-applied before the instillation of the nucleotide. Results: Ap4 has been found as a constituent of the nucleotide pool present in the aqueous humour of the rabbits. HPLC analysis permitted to confirm its identity and to calculate its concentration, this being of 197 ± 21 nM. When this nucleotide is topically applied to the rabbit eyes it produces a reduction in the intraocular pressure, which is concentration-dependent. The pD2 value calculated from the dose-response curve was 7.28 ± 0.47, which is equivalent to 52.48 nM. The time-course of such intraocular pressure reduction presented a maximal reduction to 75.1 ± 2.3 % compared to control (100%), and the effect lasted for more than 2 hours. Cross-desensitisation studies demonstrated that Ap4 effect is mediated via a P2X receptor. Antagonism with suramin, PPADS and reactive blue 2, showed that only the latter was able to revert the effect of Ap4. Antagonists of adrenoceptors and cholinoceptors were able to partially reverse the effect of this nucleotide, this indicating a partial connection with the neural mechanisms that control intraocular pressure. Conclusions: Ap4 is a physiologically relevant compound present in the aqueous humour of the rabbits, which may be used as an hypothesise compound for the treatment of ocular hytpertension.
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