title: Interaction between prostaglandin E2 and l-cis-diltiazem, a specific blocker of cyclic nucleotide gated channels in bovine aortic endothelial cells.
abstract: Prostaglandins are known to transduce their signals via 7 transmembrane prostanoid receptors, which typically signal through coupling to G proteins and downstream second messenger molecules and protein kinase activation. Recently we have shown that cyclic nucleotides affect prostaglandins binding to bovine aortic endothelial cells independent of protein kinases. Here we show that incubation of bovine aortic endothelial cells with permeable analogs of cAMP or cGMP leads to a rapid and reversible reduction in PGE(2) binding to the cells. Since cyclic nucleotides are known modulators of cyclic nucleotide gated channels, we examined the effect of a specific cyclic nucleotide gated channel blocker l-cis-diltiazem on prostaglandin E(2) (PGE(2)) binding to bovine aortic endothelial cells. L-cis-diltiazem is shown to displace PGE(2) binding to bovine aortic endothelial cells in a dose dependent manner. In addition the effect of PGE(2) and l-cis-diltiazem on thapsigargin induced calcium elevation in the cells was compared. Both agents reduced in bovine aortic endothelial cells the thapsigargin induced calcium elevation by about half. PGE(2) also retarded the time course of the response to thapsigargin. Simultaneous treatment of the cells with both PGE(2) and l-cis-diltiazem did not yield an inhibitory effect beyond that observed with l-cis-diltiazem alone. Together our data point at the cyclic nucleotide gated channels as a feasible candidate for association with the PGE(2) binding site in bovine aortic endothelial cells.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Shalom
authors.forename: Liza
authors.initials: L
authors.lastname: Barki-Harrington
authors.forename: Gilad
authors.initials: G
authors.lastname: Rimon
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004110:Diltiazem / Q000378:metabolism / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism* / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D054815:Cyclic Nucleotide-Gated Cation Channels; D004791:Enzyme Inhibitors; D007473:Ion Channels; D009712:Nucleotides, Cyclic; D019284:Thapsigargin; D000242:Cyclic AMP; D000252:Calcium-Transporting ATPases; D004110:Diltiazem; D006152:Cyclic GMP; D015232:Dinoprostone