Effects of high glucose concentration and a thromboxane synthase inhibitor on the production of thromboxane A2 and prostaglandin I2 and E2 by retinal endothelial cells.
To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2) and the effects of a thromboxane synthase inhibitor (TXSI; KDI-792; 5Z-6[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridyl methyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1 alpha as an index of PGI2. The levels of TXA2 and PGI2 were 182.3 +/- 34.3 pg/mg and 336.7 +/- 36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1 +/_ 29.7 pg/mg and 511.4 +/- 65.8 pg/mg protein at 33 mM glucose (mean +/- SD, P<0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.
Sone
H
H
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Tsukuba, Japan.
Okuda
Y
Y
Kawakami
Y
Y
Yamashita
K
K
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D004727:Endothelium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005947:Glucose / Q000032:analysis*; D011725:Pyridines / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; C096828:KDI 792; D011725:Pyridines; D011759:Pyrrolidines; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D005947:Glucose; D015232:Dinoprostone