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

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Abstract
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 [Ca2+]i. 7 The results indicate that tamoxifen interacts synergistically with ATP to activate Cl− release by the PE cells.