Phosphoinositide metabolism and prostacyclin formation in retinal microvascular endothelium: Stimulation by adenine nucleotides

Patricia L. Robertson, Diane Ar, Gary W. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphoinositide lipid metabolism and prostacyclin production are implicated in endothelium dependent vascular relaxation in large blood vessels. To determine if these biochemical pathways might be involved in the regulation of microvascular tone in the retina, we measured the formation of 6-keto-prostaglandin-F, the stable end product of prostacyclin, and inositol phosphates from 3H-labeled phosphoinositide lipids, in endothelial cells prepared from bovine retinal microvessels and maintained in long-term culture. We found that adenosine 5′-triphosphate and adenosine 5′-diphosphate both stimulated a dose-dependent accumulation of inositol phosphates and of 6-keto-prostaglandin-F in these cells. The agonist specificity of the responses, with stimulation by adenosine 5′-triphosphate and adenosine 5′-diphosphate, and inactivity of adenosine 5′-monophosphate and adenosine, suggest that they are mediated through P2 purinergic receptors. The similar early time courses of 6-keto-prostaglandin-F and inositol triphosphate production support the hypothesis that prostacyclin formation could result from the mobilization of intracellular calcium by inositol triphosphate, which activates phospholipase A, and thereby releases arachidonic acid to form prostacyclin. These findings point to a role for these cells in the regulation of normal retinal vascular tone. Because phosphoinositide lipid metabolism is altered in diabetes, dysfunction of these biochemical pathways in retinal endothelium could underlie the pathophysiology of diabetic retinopathy.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalExperimental eye research
Volume50
Issue number1
DOIs
StatePublished - Jan 1990

Keywords

  • ATP
  • phosphoinositide lipid metabolism
  • prostacyclin
  • purinergic receptor
  • retinal endothelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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