title: CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Li Ka Shing Institute of Health Sciences and Department of Physiology, Faculty of Medicine, the Chinese University of Hong Kong, China.
authors.forename: Kwong-Tai
authors.initials: KT
authors.lastname: Cheng
authors.forename: Yuk-Ki
authors.initials: YK
authors.lastname: Leung
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Yuk-Chi
authors.initials: YC
authors.lastname: Kwok
authors.forename: Ching-On
authors.initials: CO
authors.lastname: Wong
authors.forename: Hiu-Yee
authors.initials: HY
authors.lastname: Kwan
authors.forename: Yu-Bun
authors.initials: YB
authors.lastname: Man
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000634:Aminoquinolines; C518240:Cnga2 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D004791:Enzyme Inhibitors; D007097:Imines; D011743:Pyrimidines; D043704:Receptor, Adenosine A2B; D014230:Triazoles; D015124:8-Bromo Cyclic Adenosine Monophosphate; C014925:RMI 12330A; C041715:6-anilino-5,8-quinolinedione; D000262:Adenylyl Cyclases; D000241:Adenosine; D002118:Calcium