Tamoxifen and ATP synergistically activate Cl- release by cultured bovine pigmented ciliary epithelial cells.
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. 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. 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. 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. The shrinkage produced by ATP and tamoxifen was blocked by 17beta-oestradiol, but not 17alpha-oestradiol. The cooperative interaction between tamoxifen and ATP was not mediated by an enhanced rise in [Ca2+]i. The results indicate that tamoxifen interacts synergistically with ATP to activate Cl- release by the PE cells.
Mitchell
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CH
Departments of Physiology and Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. civan@mail.med.upenn.edu
Peterson-Yantorno
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K
Coca-Prados
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Civan
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MM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D007700:Kinetics; D009579:Nitrobenzoates / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; D011960:Receptors, Estrogen; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D004958:Estradiol; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D000241:Adenosine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium