Pintor Jesús, Peláez Teresa, Peral Assumpta
Departmentos de Bioquimica, Escuela Universitaria Optica, Universidad Complutense de Madrid, Spain.
J Pharmacol Exp Ther. 2004 Feb;308(2):468-73. doi: 10.1124/jpet.103.058669. Epub 2003 Nov 4.
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.
5'-四磷酸腺苷（Ap(4)）是一种存在于许多生物系统中的天然核苷酸。这种核苷酸已被发现是新西兰兔房水中核苷酸池的组成成分。高效液相色谱分析证实了其身份，并计算出其浓度水平为197±21 nM。当局部应用于兔眼时，这种单核苷酸可使眼压降低，且呈剂量依赖性。根据剂量-反应曲线计算出的pD(2)值为7.28±0.47，相当于52.48 nM。这种眼压降低的时间过程显示，与载体对照值（100%）相比，眼压最大降低至75.1±2.3%，且该效应持续超过2小时。交叉脱敏研究表明，在该系统中Ap(4)的作用是通过P2X受体介导的。P2受体拮抗剂苏拉明、6-重氮苯基-2',4'-二磺酸磷酸吡哆醛（PPADS）和活性蓝2（RB-2）表明，只有后者能够逆转Ap(4)的作用。肾上腺素能受体和胆碱能受体拮抗剂能够部分逆转这种核苷酸的作用；这可能表明其与控制眼压的神经机制有关。
