Mishima H K, Kiuchi Y, Yokoyama T, Yasumoto T, Yamazaki M
Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
Curr Eye Res. 1991 Sep;10(9):817-22. doi: 10.3109/02713689109013877.
The effects of griseolic acid (GA), a cyclic-AMP phosphodiesterase (PDE) inhibitor, and its 8'-pivaloyloxymethyl (POM) ester on intraocular pressure (IOP) in rabbits were investigated. When 50 microliters of 1 and 2% GA POM ester solutions were topically applied to one eye in normal rabbits, significant IOP decreases were detected at 2 hrs and at 1 to 5 hrs, respectively. Other than ocular hypotension, no other ocular effects were detected locally even after administration of 2% GA POM ester. A more marked reduction in IOP occurred after the intravitreal injection of the GA POM ester. IOP was also reduced when GA was used in an intravitreal injection but not when it was topically applied. The difference in permeability between GA and GA POM ester across the corneal epithelium may explain why GA failed to reduced IOP following topical administration. GA and the GA POM ester inhibited cAMP PDE in rabbit ciliary body at low concentrations, the I50 being 0.075 microM and 2.4 microM, respectively, with 0.25 microM cAMP as substrate. GA and the GA POM ester markedly increased cAMP levels in vitro in iris-ciliary body specimens. Possibly, GA POM ester or its analogues may represent a new mechanistic class of ocular hypotensive agents.
研究了环磷腺苷磷酸二酯酶（PDE）抑制剂灰黄霉素酸（GA）及其8'-新戊酰氧基甲基（POM）酯对兔眼压（IOP）的影响。将50微升1%和2%的GA POM酯溶液局部应用于正常兔的一只眼睛时，分别在2小时和1至5小时检测到眼压显著降低。除了眼压降低外，即使给予2%的GA POM酯后，局部也未检测到其他眼部效应。玻璃体内注射GA POM酯后眼压降低更为明显。玻璃体内注射GA时眼压也会降低，但局部应用时则不会。GA和GA POM酯跨角膜上皮的通透性差异可能解释了为什么局部应用GA后眼压未能降低。GA和GA POM酯在低浓度下可抑制兔睫状体中的环磷腺苷磷酸二酯酶，以0.25微摩尔/升环磷腺苷为底物时，半数抑制浓度（I50）分别为0.075微摩尔/升和2.4微摩尔/升。GA和GA POM酯在体外可显著提高虹膜-睫状体标本中的环磷腺苷水平。GA POM酯或其类似物可能代表了一类新的降眼压机制药物。
