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Abstract #10107 Published in IGR 6-1
Adenosine tetraphosphate, Ap4, a physiological regulator of intraocular pressure in normotensive rabbit eyes
Pintor J; Pelaez T; Peral AJournal of Pharmacology and Experimental Therapeutics 2004; 308: 468-473
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, and 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 (IOP), 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 IOP reduction presented a maximum decrease of IOP to 75.1-2.3% compared with the vehicle control value (100%), and the effect lasted for more than two hours. Cross-desensitization studies demonstrated that the 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 may indicate a connection with the neural mechanisms that control IOP.
Dr. J. Pintor, Depto. de Bioquim. y Biol. Molec. IV, E.U. Optica, Universidad Complutense de Madrid, c/Arcos de Jalon s/n, 28037 Madrid, Spain
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
