Methods and Results — Adenosine-induced Ca2+ influx was markedly reduced by L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated (CNG) channels, in H5V endothelial cells and primary cultured bovine aortic endothelial cells (BAECs). The Ca2+ influx was also inhibited by 2 adenylyl cyclase inhibitors MDL-12330A and SQ-22536, and by 2 A2B receptor inhibitors MRS-1754 and 8-SPT, but not by an A2A receptor inhibitor SCH-58261 or a guanylyl cyclase inhibitor ODQ. Patch clamp experiments recorded an adenosine-induced current that could be inhibited by L-cis-diltiazem and LY-83583. A CNGA2-specific siRNA markedly decreased the Ca2+ influx and the cation current in H5V cells. Furthermore, L-cis-diltiazem inhibited the endothelial Ca2+ influx in mouse aortic strips, and it also reduced 5-N-ethylcarboxamidoadenosine (NECA, an A2 adenosine receptor agonist)-induced vasorelaxation.
Conclusion — CNGA2 channels play a key role in adenosine-induced endothelial Ca2+ influx and vasorelaxation. It is likely that adenosine acts through A2B receptors and adenylyl cyclases to stimulate CNGA2.
|Number of pages||6|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Publication status||Published - May 2008|
Scopus Subject Areas
- Cardiology and Cardiovascular Medicine
- CNGA2 channels
- Endothelial cells