Inhibitory effect of sulindac on prostaglandin synthesis in cultured renal and vascular cells.
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.
Sato
M
M
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Abe
K
K
Takeuchi
K
K
Yasujima
M
M
Hagino
T
T
Fang
S
S
Kohzuki
M
M
Yoshinaga
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D013467:Sulindac / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007192:Indenes; D011453:Prostaglandins; D011458:Prostaglandins E; D013467:Sulindac; D011464:Epoprostenol; D015232:Dinoprostone