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      Diadenosine Polyphosphates Increase Cytosolic Calcium and Attenuate Angiotensin-ll-lnduced Changes of Calcium in Vascular Smooth Muscle Cells

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          The effects of diadenosine tetraphosphate (AP<sub>4</sub>A), diadenosine pentaphosphate (AP<sub>5</sub>A), and diadenosine hexaphosphate (AP<sub>6</sub>A) on the cytosolic free calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye technique. A concentration-dependent increase of [Ca<sup>2+</sup>]<sub>i</sub> by AP<sub>4</sub>A, AP<sub>5</sub>A, and AP<sub>6</sub>A was observed in VSMC. Additions of 10 µmol/l AP<sub>4</sub>A, AP<sub>5</sub>A, and AP<sub>6</sub>A significantly increased [Ca<sup>2+</sup>]<sub>i</sub> in VSMC by 224 ± 62 nmol/l (n = 6; p < 0.01,205 ± 27 nmol/l (n = 14; p < 0.01), and 269 ± 98 nmol/l (n = 5; p < 0.05), respectively. Additions of AP4A, AP5A, and AP<sub>6</sub>A only 120 s prior to angiotensin II (Ang II) administration significantly attenuated the Ang-II-induced changes of [Ca<sup>2+</sup>]<sub>i</sub> in VSMC from 1,053 ± 174 nmol/l to 283 ± 42 nmol/l, 591 ± 112 nmol/l, and 477 ± 79 nmol/l, respectively (each p < 0.01 as compared to the control). The AP<sub>6</sub>A-induced changes of [Ca<sup>2+</sup>]<sub>i</sub> were inhibited by the blockers of P2 purinoceptors, suramin and pyridoxal-phosphate-6-azophenyl-2’,4<sup>/</sup>-disulphonic acid, but not by the inhibitor of P2y purinoceptors, reactive blue. Adenosine triphosphate (ATP) also increased [Ca<sup>2+</sup>]<sub>i</sub> in VSMC, whereas the purinoceptor P2x agonist, αβ-methylene-ATP, had no effect on [Ca<sup>2+</sup>]<sub>i</sub> in VSMC. Therefore diadenosine polyphosphates may induce changes of [Ca<sup>2+</sup>]<sub>i</sub> by interacting with purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca<sup>2+</sup>-dependent contractile response of VSMC.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 2
          : 132-138
          Medizinische Poliklinik, University of Münster, Germany
          159141 J Vasc Res 1996;33:132–138
          © 1996 S. Karger AG, Basel

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          Pages: 7
          Research Paper


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