Genistein, a tyrosine kinase inhibitor, reduces Ca2+ mobilization in swine carotid media.
DiSalvo and colleagues (Biochem. Biophys. Res. Commun. 190: 968-974, 1993) found that tyrosine kinase inhibitors reduced force at constant Ca2+ concentrations in permeabilized mesenteric arterioles. These data suggest that tyrosine kinase activation could regulate Ca2+ sensitivity in intact vascular smooth muscle. We tested this hypothesis by examining the effects of the tyrosine kinase inhibitor genistein on intracellular Ca2+ concentration ([Ca2+]i), myosin regulatory light chain (MRLC) phosphorylation, and isometric stress in intact swine carotid media tissues. Pretreatment with 30 microM genistein attenuated histamine-induced increases in [Ca2+]i (estimated using the photoprotein aequorin), MRLC phosphorylation, and stress. The genistein-dependent decrease in [Ca2+]i quantitatively accounted for the decrease in MRLC phosphorylation and stress. There was no measurable change in the Ca2+ dependence of MRLC phosphorylation or the dependence of force on MRLC phosphorylation. Genistein inhibited contractions independently of the source of activator Ca2+. These data suggest that tyrosine kinase(s) may influence force development in the intact swine carotid media by altering [Ca2+]i rather than modulating the Ca2+ sensitivity of MRLC phosphorylation.
Gould
E M
EM
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville 22908, USA.
Rembold
C M
CM
Murphy
R A
RA
D000331:Aequorin; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013552:Swine; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D007529:Isoflavones; D000331:Aequorin; D004533:Egtazic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D009218:Myosins; D002122:Calcium Chloride; D002118:Calcium; D004121:Dimethyl Sulfoxide