Details
| Original language | English |
|---|---|
| Pages (from-to) | 79-84 |
| Number of pages | 6 |
| Journal | Journal of Bioenergetics and Biomembranes |
| Volume | 42 |
| Issue number | 1 |
| Publication status | Published - Feb 2010 |
Abstract
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 microM) 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.
Keywords
- Animals, Cattle, Cell Line, Connexins/metabolism, Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors, Dipyridamole/pharmacology, Endothelial Cells/drug effects, Fibrinolytic Agents/pharmacology, Gap Junctions/drug effects, Isoquinolines/pharmacology, Models, Biological, Protein Kinase Inhibitors/pharmacology, Sulfonamides/pharmacology
Sustainable Development Goals
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In: Journal of Bioenergetics and Biomembranes, Vol. 42, No. 1, 02.2010, p. 79-84.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Dipyridamole increases gap junction coupling in bovine GM-7373 aortic endothelial cells by a cAMP-protein kinase A dependent pathway
AU - Begandt, D
AU - Bintig, W
AU - Oberheide, K
AU - Schlie, S
AU - Ngezahayo, A
N1 - Funding information: The work was supported by Boehringer Ingel-heim International GmbH.
PY - 2010/2
Y1 - 2010/2
N2 - 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 microM) 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.
AB - 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 microM) 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.
KW - Animals
KW - Cattle
KW - Cell Line
KW - Connexins/metabolism
KW - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
KW - Dipyridamole/pharmacology
KW - Endothelial Cells/drug effects
KW - Fibrinolytic Agents/pharmacology
KW - Gap Junctions/drug effects
KW - Isoquinolines/pharmacology
KW - Models, Biological
KW - Protein Kinase Inhibitors/pharmacology
KW - Sulfonamides/pharmacology
U2 - 10.1007/s10863-009-9262-2
DO - 10.1007/s10863-009-9262-2
M3 - Article
C2 - 20054624
VL - 42
SP - 79
EP - 84
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
SN - 0145-479X
IS - 1
ER -