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(Stroke. 2000;31:1377.)
© 2000 American Heart Association, Inc.

Original Contributions

Mechanism of ATP-Induced [Ca²⁺]_i Mobilization in Rat Basilar Smooth Muscle Cells

Kazuya Aoki, MD; Alexander Y. Zubkov, MD; Andrew D. Parent, MD John H. Zhang, MD, PhD

From the Department of Neurosurgery, University of Mississippi Medical Center, Jackson.

Correspondence to John H. Zhang, MD, PhD, Department of Neurosurgery, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. E-mail jzhang{at}neurosurgery.umsmed.edu

Background and Purpose—We have previously reported that extracellular ATP activates P_2u receptors and increases intracellular free Ca²⁺ ([Ca²⁺]_i) by G protein/phospholipase C/inositol 1,4,5-triphosphate pathways in cerebral artery smooth muscle cells. However, the possible contribution of other signaling pathways remains unclear. This study was undertaken to investigate the role of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in mediating ATP-induced Ca²⁺ mobilization in rat basilar artery smooth muscle cells (RBASMCs).

Methods—RBASMCs were freshly isolated, and [Ca²⁺]_i was monitored by fura 2 microfluorimetry. MAPK phosphorylation was studied by the Western blot technique.

Results—ATP produced a biphasic [Ca²⁺]_i response, which consists of releasing Ca²⁺ from internal stores and influx from extracellular space. PTK inhibitors tyrphostin 51 and genistein inhibited [Ca²⁺]_i response to ATP. Tyrphostin A1, an inactive analogue of tyrphostins, failed to reduce the ATP-induced response. MAPK kinase inhibitor PD98059, but not U0126, reduced the ATP-induced [Ca²⁺]_i response. Phosphatidylinositol 3-kinase (PI3-K) tyrosine kinase inhibitor wortmannin, but not janus tyrosine kinase (JAK2) inhibitor AG490, partially inhibited the [Ca²⁺]_i response induced by ATP. In addition, ATP enhanced MAPK phosphorylation in a concentration- and time-dependent manner, and genistein, tyrphostin 51, PD98059, and U0126 inhibited MAPK phosphorylation.

Conclusions—Extracellular ATP produced [Ca²⁺]_i elevation and MAPK phosphorylation in RBASMCs, and the effect was regulated by PTK. The role of MAPK in ATP-induced [Ca²⁺]_i elevation is not clear. PI3-K tyrosine kinase and JAK2 tyrosine kinase may not play an important role in the ATP-induced [Ca²⁺]_i response in RBASMCs.

Editorial Comment

R. Loch Macdonald, MD, PhD, Guest Editor

Section of Neurosurgery University of Chicago Medical Center Chicago, Illinois

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