Identification of functional PGH2/TxA2 receptors on human endothelial cells

K. Craig Kent, Laura J. Collins, Francis T. Schwerin, Malay K. Raychowdhury, J. Anthony Ware

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Although functional receptors for thromboxane A2 and prostaglandin H2 (TxA2/PGH2) have been identified in platelets and vascular smooth muscle cells, receptor-mediated events in human endothelial cells stimulated by these endoperoxides have not been shown. Using cultured endothelial cells harvested from human umbilical or saphenous veins, we measured the effect of the TxA2 mimetic U46619 on mobilization of cytoplasmic calcium ([Ca2+]i), as well as release of prostacyclin and expression of the proto-oncogene c-fos, intracellular events that have been linked to [Ca2+]i rise in stimulated endothelial cells. Addition of U46619 to confluent fura 2-loaded endothelial cells caused a concentration-dependent rise in intracellular [Ca2+]i, with agonist concentrations of 300 nM producing a maximal [Ca2+]i rise. This [Ca2+]i rise was a uniform response observed in all individual endothelial cells throughout the monolayer, as shown by microspectrofluorimetric visualization. Similar effects were seen with a structurally dissimilar endoperoxide analogue, I-BOP, and with the naturally occurring endoperoxide PGH2. The initial [Ca2+]i rise was not reduced when extracellular [Ca2+]i was chelated with EGTA, but a later "plateau" phase was eliminated. An antagonist of the receptor for TxA2/PGH2 (SQ29548) strongly inhibited [Ca2+]i mobilization. Stimulation of endothelial cells with U46619 also transiently increased expression of the proto-oncogene c-fos, as determined by RNA hybridization, and induced a fivefold increase in prostacyclin release. Thus, endoperoxides can stimulate human venous endothelial cells by means of TxA2/PGH2 receptors, whose occupancy can activate intracellular events associated with functional changes.

Original languageEnglish (US)
Pages (from-to)958-965
Number of pages8
JournalCirculation Research
Volume72
Issue number5
StatePublished - May 1993

Fingerprint

Prostaglandin H2 Receptors Thromboxane A2
Endothelial Cells
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
fos Genes
Epoprostenol
Prostaglandin H2
Umbilical Veins
Fura-2
Egtazic Acid
Saphenous Vein
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cultured Cells
Blood Platelets
RNA
Calcium

Keywords

  • c-fos
  • Calcium
  • Endothelium
  • Receptor
  • Thromboxane A

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kent, K. C., Collins, L. J., Schwerin, F. T., Raychowdhury, M. K., & Ware, J. A. (1993). Identification of functional PGH2/TxA2 receptors on human endothelial cells. Circulation Research, 72(5), 958-965.

Identification of functional PGH2/TxA2 receptors on human endothelial cells. / Kent, K. Craig; Collins, Laura J.; Schwerin, Francis T.; Raychowdhury, Malay K.; Ware, J. Anthony.

In: Circulation Research, Vol. 72, No. 5, 05.1993, p. 958-965.

Research output: Contribution to journalArticle

Kent, KC, Collins, LJ, Schwerin, FT, Raychowdhury, MK & Ware, JA 1993, 'Identification of functional PGH2/TxA2 receptors on human endothelial cells', Circulation Research, vol. 72, no. 5, pp. 958-965.
Kent KC, Collins LJ, Schwerin FT, Raychowdhury MK, Ware JA. Identification of functional PGH2/TxA2 receptors on human endothelial cells. Circulation Research. 1993 May;72(5):958-965.
Kent, K. Craig ; Collins, Laura J. ; Schwerin, Francis T. ; Raychowdhury, Malay K. ; Ware, J. Anthony. / Identification of functional PGH2/TxA2 receptors on human endothelial cells. In: Circulation Research. 1993 ; Vol. 72, No. 5. pp. 958-965.
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