Stroke/Cerebral Vasospasm

S. Iwabuchi

Tyrosine kinases are functionally classified in to three group; tyrosine kinases associated with cell surface receptors (group 1), the focal adhesion kinase (group 2) and nucleus tyrosine kinases (group 3). Smooth muscle contraction may be modified by the receptor tyrosine kinase (group 1A) or receptor-coupled tyrosine kinases (group 1B).Hemolysate released from blood clots contains oxyhemoglobin and ATP etc. We supposed that these erythrocyte components binds the receptors and activates tyrosine kinase, PLC(phospholipase C)g. PLCg hydrolyzes PIP2(phosphatidylinositol-4,5-bisphosphate) and generates IP3(D-myo-inositol-1,4,5-trisphosphate) and DG(diacylglycerol).

Your question about the difference between smooth muscle cells and endothelial cells is also really good point. Previously, Dr. Marton reported the [Ca2+]i response to hemolysate in endothelial cells. The initial peak in endothelial cells was unchanged in Ca2+ free solution. Hence, the peak was solely the peak was solely due to store release in endothelial cells. The role of tyrosine kinase in not the same either, between endothelial cells and smooth muscle cells. Although, tyrosine kinase inhibitors reduced the [Ca2+]i peak response to hemolysate in the smooth muscle cells, the endothelial peak was unchanged. Tyrosine kinase inhibitors nearly completely eliminated the plateau phase in endothelial cells, however, it only caused a partial inhibition of the plateau in smooth muscle cells.Therefore, we suppose that the [Ca2+]i responses to hemolysate appear to be identical in endothelial  and smooth muscle cells and the controlling mechanisms are distinct.

Satoshi Iwabuchi


On Fri Dec 4, grover wrote
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>Dr. Iwabuchi:Hope you are enjoying the meeting.  Great poster. I was wondering what your thoughts are on how hemolysate molecules (<10 kDa) affect tyrosine kinase - directly or indirectly. Essentially then I am asking if the hemolysate would produce the phosphorylation in the cell regardless of the cell type but the consequences in smooth muscle and endothelium may differ downstream of the tyrosine phosphorylation.
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