Role of store-operated Ca(2+) entry in adenosine-induced vasodilatation of rat small mesenteric artery.
Store-operated Ca(2+) entry (SOCE) has recently been proposed to contribute to Ca(2+) influx in vascular smooth muscle cells (VSMCs). Adenosine is known for its protective role against hypoxia and ischemia by increasing nutrient and oxygen supply through vasodilation. This study was designed to examine the hypothesis that SOCE have a functional role in adenosine-induced vasodilation. Small mesenteric resistance arteries and mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery rings were measured by a sensitive myograph system. Laser-scanning confocal microscopy was used to determine the intracellular Ca(2+) concentration of fluo 3-loaded VSMCs. Adenosine (0.1-100 microM) relaxed artery rings that were precontracted by phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs, passive store depletion by thapsigargin and active store depletion by phenylephrine both induced Ca(2+) influx due to SOCE. Adenosine inhibited SOCE-mediated increases in cytosolic Ca(2+) levels evoked by the emptying of the stores. In isolated artery rings, adenosine inhibited SOCE-induced contractions due to store depletion. A(2A) receptor antagonism with SCH-58261 and adenylate cyclase inhibition with SQ-22536 largely attenuated adenosine responses. The cAMP analog 8-bromo-cAMP mimicked the effects of adenosine on SOCE. Our results indicate a novel mechanism of vasodilatation by adenosine that involves regulation of SOCE through the cAMP signaling pathway due to activation of adenosine A(2A) receptors.
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
Shengpeng
S
Wang
Yan
Y
Zhang
W Gil
WG
Wier
Xiaojiang
X
Yu
Ming
M
Zhao
Hao
H
Hu
Lei
L
Sun
Xi
X
He
Youhua
Y
Wang
Bing
B
Wang
Weijin
W
Zang
D000241:Adenosine / Q000494:pharmacology*; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D014665:Vasodilator Agents; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium