Bito L Z, Salvador E V
J Pharmacol Exp Ther. 1976 Aug;198(2):481-8.
The inhibitory effects of drugs on prostaglandin biotransport were studied by measuring the concentrative accumulation of 3H by rabbit choroid plexuses, segments of anterior uvea and kidney cortex slices after incubation in tissue culture medium containing 3H-prostaglandin F2 alpha. After 10 minutes of incubation in the absence of an inhibitor, the choroid plexus showed a tissue/medium 3H accumulation ratio of 14 +/- 0.7; after 30 minutes of incubation, the anterior uvea and the kidney cortex slices showed accumulation ratios of 6.4 +/- 0.5 and 5.6 +/- 0.1, respectively. The I50 values for inhibition of 3H accumulation by indomethacin were 10, 8 and 12 muM for the three tissues, respectively. Some related drugs-oxyphenbutazone, D-naproxen, l-naproxen, ibuprofen, phenylbutazone and pirprofen-were also found to be effective inhibitors of 3H accumulation (I50 for anterior uvea, 6-28 muM) whereas aspirin, dexamethasone phosphate and penicillin had an inhibitory effect only at much higher concentrations (I50 0.1-2.0 mM). Papaverine, fursemide and probenecid were approximately as effective as the anti-inflammatory organic acids (I50 0.01-0.1 mM), whereas bromcresol green was at least 10-fold more effective. Diphenhydramine and the nonacidic prostaglandin synthesis inhibitors, phenelzine and paracetamol, showed little (I50 greater than 1 mM) or no inhibitory effect. The inhibition of this transport system by some drugs, most notably nonsteroidal anti-inflammatory organic acids, and consequent alterations in the distribution and disposition of prostaglandins must be taken into account in the development of new anti-inflammatory agents and in the interpretation of the mechansim of action and side effects of such drugs.
通过在含有³H - 前列腺素F2α的组织培养基中孵育后，测量兔脉络丛、前葡萄膜段和肾皮质切片对³H的浓缩积累，研究了药物对前列腺素生物转运的抑制作用。在无抑制剂的情况下孵育10分钟后，脉络丛的组织/培养基³H积累比为14±0.7；孵育30分钟后，前葡萄膜和肾皮质切片的积累比分别为6.4±0.5和5.6±0.1。吲哚美辛对这三种组织³H积累抑制的半数抑制浓度（I50）分别为10、8和12μM。还发现一些相关药物——羟苯丁宗、右旋萘普生、左旋萘普生、布洛芬、保泰松和吡洛芬——也是³H积累的有效抑制剂（前葡萄膜的I50为6 - 28μM），而阿司匹林、地塞米松磷酸酯和青霉素仅在高得多的浓度下才有抑制作用（I50为0.1 - 2.0 mM）。罂粟碱、速尿和丙磺舒的效果与抗炎有机酸大致相同（I50为0.01 - 0.1 mM），而溴甲酚绿的效果至少强10倍。苯海拉明以及非酸性前列腺素合成抑制剂苯乙肼和对乙酰氨基酚几乎没有（I50大于1 mM）或没有抑制作用。在开发新的抗炎药物以及解释此类药物的作用机制和副作用时，必须考虑某些药物对该转运系统的抑制作用，尤其是非甾体抗炎有机酸，以及由此导致的前列腺素分布和处置的改变。
