Dipyridamole increases gap junction coupling in bovine GM-7373 aortic endothelial cells by a cAMP-protein kinase A dependent pathway
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The scrape-loading/dye transfer technique was applied on the bovine aortic endothelial cell line GM-7373 to analyze the effects of the antithrombolytic drug dipyridamole on gap junction coupling in endothelial cells. We found that a cell treatment for 24 h with dipyridamole in therapeutically relevant concentrations (1–100 µM) increased gap junction coupling in a dose dependent manner. Similar to dipyridamole, forskolin as well as 8-Br-cAMP increased the gap junction coupling, while dibutyryl-cGMP (db-cGMP) did not affect the gap junction coupling of the GM-7373 endothelial cells. In parallel, a pharmacological inhibition of protein kinase A (PKA) with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89), antagonised the action of dipyridamole on gap junction coupling. We propose that the observed dipyridamole induced increase in gap junction coupling in endothelial cells is related to a cAMP-PKA dependent phosphorylation pathway. The report shows that gap junction coupling in endothelial cells is a suitable therapeutic target for treatment of cardiovascular diseases.
KeywordsDipyridamole Endothelial cells Gap junction Connexins Scrape loading cAMP PKA H-89
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- Cruciani V, Mikalsen SO (2002) Biol. Cell 94:433–443Google Scholar
- De Wit C, Roos F, Bolz SS, Kirchhoff S, Krüger O, Willecke K, Pohl U (2000) Circ Res 86:649–655Google Scholar
- De Wit C, Roos F, Bolz SS, Pohl U (2003) Physiol Genomics 13:169–177Google Scholar
- Figueroa XF, Isakson BE, Duling BR (2004) Physiology (Bethesda) 19:277–284Google Scholar
- Harris AL (2001) Q Rev Biophys 34:325–472Google Scholar
- Schmidt VJ, Wölfle SE, Boettcher M, de Wit C (2008) Pharmacol Rep 60:68–74Google Scholar