舒林酸对培养的肾细胞和血管细胞中前列腺素合成的抑制作用。

Inhibitory effect of sulindac on prostaglandin synthesis in cultured renal and vascular cells.

作者信息

Sato M, Abe K, Takeuchi K, Yasujima M, Hagino T, Fang S, Kohzuki M, Yoshinaga K

机构信息

Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

出版信息

Agents Actions Suppl. 1987;22:37-42. doi: 10.1007/978-3-0348-9299-5_3.

DOI:10.1007/978-3-0348-9299-5_3

PMID:3324718

Abstract

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is said to be less toxic to the kidney than the other NSAIDs. To examine this hypothesis we investigated the effects of sulindac and other NSAIDs on prostaglandin (PG) synthesis in cultured rat renal and vascular cells. In all cells examined, indomethacin, tiaprofenic acid, aspirin and ibuprofen (3.3 x 10(-5)-3.3 x 10(-4)M) inhibited both basal and arachidonic acid (AA)-stimulated PGE2 or PGI2 synthesis (measured as 6-keto-PGF1 alpha), while sulindac (3.3 x 10(-5)-3.3 x 10(-4)M) inhibited both basal and AA-stimulated PGE2 synthesis in renal papillary collecting tubule cells but not basal PGI2 synthesis in vascular smooth muscle cells or AA-stimulated PGE2 synthesis in glomerular mesangial cells. The order of potency for NSAIDs to inhibit PG synthesis in these cells was tiaprofenic acid, indomethacin greater than ibuprofen, aspirin greater than sulindac. It is suggested that the prodrug sulindac is biotransformed to the active sulfide in the intact kidney cells, which may be less prominent in glomerular mesangial or vascular smooth muscle cells.

摘要

舒林酸是一种非甾体抗炎药（NSAID），据说它对肾脏的毒性比其他非甾体抗炎药小。为了验证这一假设，我们研究了舒林酸和其他非甾体抗炎药对培养的大鼠肾细胞和血管细胞中前列腺素（PG）合成的影响。在所有检测的细胞中，吲哚美辛、噻洛芬酸、阿司匹林和布洛芬（3.3×10⁻⁵ - 3.3×10⁻⁴M）均抑制基础状态和花生四烯酸（AA）刺激的PGE₂或PGI₂合成（以6-酮-PGF1α衡量），而舒林酸（3.3×10⁻⁵ - 3.3×10⁻⁴M）抑制肾乳头集合管细胞中基础状态和AA刺激的PGE₂合成，但不抑制血管平滑肌细胞中基础状态的PGI₂合成，也不抑制肾小球系膜细胞中AA刺激的PGE₂合成。在这些细胞中，非甾体抗炎药抑制PG合成的效力顺序为：噻洛芬酸、吲哚美辛＞布洛芬、阿司匹林＞舒林酸。提示前体药物舒林酸在完整的肾细胞中可生物转化为活性硫化物，而在肾小球系膜或血管平滑肌细胞中这种转化可能不那么明显。