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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 4, 2003; DOI: 10.1124/jpet.103.058669

0022-3565/04/3082-468-473$20.00
JPET 308:468-473, 2004
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CELLULAR AND MOLECULAR

Adenosine Tetraphosphate, Ap4, a Physiological Regulator of Intraocular Pressure in Normotensive Rabbit Eyes

Jesús Pintor, Teresa Peláez, and Assumpta Peral

Departmentos de Bioquimica (J.P., T.P.) and Optica (A.P.), Escuela Universitaria Optica, Universidad Complutense de Madrid, Madrid, Spain

Adenosine 5' tetraphosphate, Ap4, is a natural nucleotide present in many biological systems. This nucleotide has been found as a constituent of the nucleotide pool present in the aqueous humor of New Zealand rabbits. HPLC analysis confirmed its identity and calculated its concentration levels to be 197 ± 21 nM. When applied topically to the rabbit eyes, this mononucleotide produced a reduction in the intraocular pressure, which was dose-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 decrease of IOP to 75.1 ± 2.3% compared with the vehicle control value (100%), and the effect lasted for more than 2 h. Cross-desensitization studies demonstrated that Ap4 effect was mediated via a P2X receptor in this system. P2 receptor antagonists suramin, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS), and reactive blue 2 (RB-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 might indicate a connection with the neural mechanisms that control the intraocular pressure.

Received August 14, 2003; accepted October 31, 2003.

Address correspondence to: Dr. Jesus Pintor, Departmento de Bioquimica y Biologia Molecular IV, E.U. Optica, Universidad Complutense de Madrid, c/Arcos de Jalon s/n, 28037 Madrid, Spain. E-mail: jpintor{at}vet.ucm.es




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