Affiliation:
1. From the Li Ka Shing Institute of Health Sciences and Department of Physiology, Faculty of Medicine, the Chinese University of Hong Kong, China.
Abstract
Objectives—
Adenosine is a cAMP-elevating vasodilator that induces both endothelium-dependent and -independent vasorelaxation. An increase in cytosolic Ca
2+
([Ca
2+
]
i
) is a crucial early signal in the endothelium-dependent relaxation elicited by adenosine. This study explored the molecular identity of channels that mediate adenosine-induced Ca
2+
influx in vascular endothelial cells.
Methods and Results—
Adenosine-induced Ca
2+
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 Ca
2+
influx was also inhibited by 2 adenylyl cyclase inhibitors MDL-12330A and SQ-22536, and by 2 A
2B
receptor inhibitors MRS-1754 and 8-SPT, but not by an A
2A
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 Ca
2+
influx and the cation current in H5V cells. Furthermore, L-
cis
-diltiazem inhibited the endothelial Ca
2+
influx in mouse aortic strips, and it also reduced 5-
N
-ethylcarboxamidoadenosine (NECA, an A
2
adenosine receptor agonist)-induced vasorelaxation.
Conclusion—
CNGA2 channels play a key role in adenosine-induced endothelial Ca
2+
influx and vasorelaxation. It is likely that adenosine acts through A
2B
receptors and adenylyl cyclases to stimulate CNGA2.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
22 articles.
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