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

Life Sci. 1996;58(3):239-43. doi: 10.1016/0024-3205(95)02281-3.

Abstract

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.

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Dinoprostone / biosynthesis*
  • Endothelium / metabolism
  • Enzyme Inhibitors / metabolism*
  • Epoprostenol / biosynthesis*
  • Glucose / analysis*
  • Pyridines / metabolism*
  • Pyrrolidines / metabolism*
  • Retina / metabolism*
  • Thromboxane A2 / biosynthesis*
  • Thromboxane-A Synthase / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • KDI 792
  • Pyridines
  • Pyrrolidines
  • Thromboxane A2
  • Epoprostenol
  • Thromboxane-A Synthase
  • Glucose
  • Dinoprostone