Adenosine tetraphosphate, Ap4, a physiological regulator of intraocular pressure in normotensive rabbit eyes

Adenosine 5' tetraphosphate, Ap(4), 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 pD(2) 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 Ap(4) 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 Ap(4). 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.