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Src Family Tyrosine Kinases Mediate Contraction of Rat Isolated Tail Arteries in Response to a Hyposmotic Stimulus

Src Family Tyrosine Kinases Mediate Contraction of Rat Isolated Tail Arteries in Response to a Hyposmotic Stimulus

Sumangali Wijetunge, Alun D Hughes

J Hypertens. 2007 Sep;25(9):1871-8.

PMID: 17762651

Abstract:

Objective:
Hypotonic solutions cause vasoconstriction in rat tail arteries, due largely to activation of L-type calcium channels (CaV1.2). We studied possible roles of tyrosine kinases, particularly src family kinases (SFK) and extracellular signal-related kinases (ERK1/2), in this response.
Methods:
Rat tail arteries were mounted on a myograph for measurement of isometric force. Arteries were bathed in isosmotic physiological saline solution (300 mOsm/l) containing 50 mmol/l mannitol and were stimulated by a hyposmotic solution containing 0 mmol/l mannitol (PSS-M). Activation of tyrosine kinases and ERK1/2 by hyposmotic solution was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting on rat tail artery lysates with specific phospho-antibodies.
Results:
Western blotting showed SFK src and yes present in rat tail artery. PSS-M increased tyrosine phosphorylation of several proteins, including SFK and ERK1/2. Genistein blocked phosphorylation of SFK and ERK1/2 by PSS-M. In isolated arteries PSS-M caused a contraction inhibited by the tyrosine kinase inhibitor, genistein, and three structurally different selective SFK inhibitors, herbimycin-A, PP1 and SU6656. Mitogen-activated protein kinase kinase inhibitor PD98059 or selective inhibitors of platelet-derived growth factor receptor (AG1296) and epidermal growth factor receptor (AG1478) had no effect on contraction induced by a hypotonic solution.
Conclusions:
Hyposmotic conditions activate SFK, src and yes, and contract rat tail artery by a SFK-dependent mechanism. ERK1/2 are activated by the hypotonic solution, but do not play a role in the contractile response. SFK modulation of CaV1.2 may be an important mechanism mediating vasoconstriction to mechanical stimuli in vascular smooth muscle.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415688	InSolution Src Inhibitor, PP1			Price
IAR42415696	InSolution SU6656			Price

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