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

1. Purines alter aqueous humour secretion by the bilayered ciliary epitheli um. Adenosine but not ATP shrinks non-pigmented ciliary epithelial (NPE) ce lls by activating Cl- channels. The 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. Neithe r ATP nor tamoxifen alone had a consistent effect on cell volume. 3. The tamoxifen, ATP-activated shrinkage required Cl- release since the re sponse was blocked by removing Cl- and was inhibited by the Cl- channel blo ckers 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 p rotein kinase C (PKC) or calcium-calmodulin, or that it acts on histamine o r carbachol receptors. 5. The shrinkage produced by ATP and tamoxifen was blocked by 17 beta-oestr adiol, but not 17 alpha-oestradiol. 6. The cooperative interaction between tamoxifen and ATP was not mediated b y an enhanced rise in [Ca2+](i). 7. The results indicate that tamoxifen interacts synergistically with ATP t o activate Cl- release by the PE cells.