Expression and responsiveness of P2Y2 receptors in human endometrial cancer cell lines

Ann C. Katzur, Taka Aki Koshimizu, Melanija Tomić, Askan Schultze-Mosgau, Olaf Ortmann, Stanko S. Stojilkovic*

*Corresponding author for this work
38 Citations (Scopus)

Abstract

In single endometrial carcinoma HEC-1A and Ishikawa cells, ATP induced a rapid and extracellular Ca2+-independent rise in cytosolic Ca2+ concentration ([Ca2+](i)) in a dose-dependent manner, with an ED50 of about 10 μM. The spike phase was followed by a sustained plateau phase that was dependent on Ca2+ influx through voltage-insensitive Ca2+ channels, whose gating was controlled by a capacitative Ca2+ entry mechanism. ADP was less potent in raising the cystolic Ca2+ concentration, and AMP and adenosine were ineffective. The order of agonist potency for this receptor was ATP = UTP > ATP-γ-S>>ADP. Several other agonists, including β,γ-methylene-ATP, 2-MeS-ATP, and BzATP were ineffective. This ligand-selective profile indicates the expression of the P2Y2R subtype in endometrial cells. Accordingly, reverse transcription-PCR using P2Y2 primers amplified the expected transcript from both cell lines. The coupling of these receptors to phospholipase C was confirmed by the ability of ATP to increase inositol 1,4,5-trisphosphate and diacylglycerol productions. These receptors are also coupled to the phospholipase D-1 pathway, leading to accumulation of phosphatidic acid. Activation of P2Y2 receptors by a slowly degradable ATP analog, ATP-γ-S, was associated with a significant suppression of cell proliferation without affecting the cellular apoptosis. These results indicate that P2Y2 receptors may participate in control of the cell cycle of endometrial carcinoma cells.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number11
Pages (from-to)4085-4091
Number of pages7
ISSN0021-972X
DOIs
Publication statusPublished - 1999

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