Evidence for the existence of F2-isoprostane receptors on rat vascular smooth muscle cells

M. Fukunaga, N. Makita, L. J. Roberts, J. D. Morrow, K. Takahashi, K. F. Badr

Research output: Contribution to journalArticlepeer-review

Abstract

The isoprostanes are nonenzymatically generated prostanoids synthesized in vivo in humans and rats through reactions catalyzed by free oxygen radicals. 8-Epi-prostaglandin F(2α) (8-epi-PGF(2α)), an F2-isoprostane, is a potent smooth muscle constrictor. A thromboxane A2 (TxA2) receptor antagonist, SQ 29548, blocks renal vasoconstriction during 8-epi-PGF(2α) administration in rats. With the use of cultured rat aortic smooth muscle cells, we found specific binding sites for [3H]SQ 29548 and for [125I]BOP, a TxA2 agonist. Both ligands were displaced from these binding sites by 8-epi- PGF(2α), although with significantly lesser potency than nonlabeled SQ 29548, I-BOP, or U-46619, a TxA2 agonist. In contrast, 8-epi-PGF(2α) stimulated inositol 1,4,5-trisphosphate production and DNA synthesis in these cells with significantly greater potency than any TxA2 agonist, effects only partially inhibited by SQ 29548. In human TxA2 receptor cDNA-transfected cells, competition by 8-epi-PGF(2α) for specific [3H]SQ 29548 binding was negligible. Thus 8-epi-PGF(2α) probably exerts its biological actions in vascular smooth muscle through activation of receptor sites related to but distinct from TxA2 receptors. The existence of such binding sites suggests novel avenues for investigation into the biology of TxA2 and of free radical-mediated tissue injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume264
Issue number6 33-6
StatePublished - 1993
Externally publishedYes

Keywords

  • isoprostanes
  • phosphoinositide turnover
  • thromboxane A
  • thromboxane receptor

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

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