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.
Pintor
Jesús
J
Departmentos de Bioquimica, Escuela Universitaria Optica, Universidad Complutense de Madrid, Spain. jpintor@vet.ucm.es
Peláez
Teresa
T
Peral
Assumpta
A
D000227:Adenine Nucleotides / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits
D000227:Adenine Nucleotides; D018680:Cholinergic Antagonists; D058919:Purinergic P2 Receptor Antagonists; C017991:adenosine 5'-tetraphosphate