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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/H347    most recent 00060.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, S. Articles by Zang, W. PubMed PubMed Citation Articles by Wang, S. Articles by Zang, W.

Role of store-operated Ca²⁺ entry in adenosine-induced vasodilatation of rat small mesenteric artery

Departments of ¹Pharmacology and ²Pharmacy, School of Medicine, Xi'an Jiaotong University, Xi'an, Peoples Republic of China; and ³Departments of Physiology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 16 January 2009 ; accepted in final form 29 April 2009

Store-operated Ca²⁺ entry (SOCE) has recently been proposed to contribute to Ca²⁺ 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 Ca²⁺ concentration of fluo 3-loaded VSMCs. Adenosine (0.1–100 µM) 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 Ca²⁺ influx due to SOCE. Adenosine inhibited SOCE-mediated increases in cytosolic Ca²⁺ 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.

adenosine receptor; capacitative calcium ion entry; vasorelaxation