Tamoxifen and ATP synergistically activate Cl − release by cultured bovine pigmented ciliary epithelial cells

1 Purines alter aqueous humour secretion by the bilayered ciliary epithelium. Adenosine but not ATP shrinks non‐pigmented ciliary epithelial (NPE) cells by activating Cl − channels. We now report effects of ATP on pigmented ciliary epithelial (PE) cells. 2 Cultured bovine PE cells were studied volumetrically by electronic cell sorting. ATP and tamoxifen acted synergistically to shrink PE cells. Neither ATP nor tamoxifen alone had a consistent effect on cell volume. 3 The tamoxifen, ATP‐activated shrinkage required Cl − release since the response was blocked by removing Cl − and was inhibited by the Cl − channel blockers 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate and 4,4′‐diisothiocyano‐2,2′‐disulfonic acid. 4 The modulating effect of tamoxifen could have reflected many actions of tamoxifen. Our data do not support the suggestion that tamoxifen inhibits protein kinase C (PKC) or calcium‐calmodulin, or that it acts on histamine or carbachol receptors. 5 The shrinkage produced by ATP and tamoxifen was blocked by 17β‐oestradiol, but not 17α‐oestradiol. 6 The cooperative interaction between tamoxifen and ATP was not mediated by an enhanced rise in [Ca 2+ ] i . 7 The results indicate that tamoxifen interacts synergistically with ATP to activate Cl − release by the PE cells.