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

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Abstract
Background and Purpose—We have previously reported that extracellular ATP activates P2u 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 resp...

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