G proteins and phospholipase C mediate thrombin-induced generation of plasminogen activator inhibitor-1 from vascular smooth muscle cells

Journal of Vascular Research
S RenG X Shen

Abstract

The present study investigated transcellular signalling mechanism involved in thrombin-induced production of plasminogen activator inhibitor-1 (PAI-1) in cultured vascular baboon aortic smooth muscle cells (BASMC). Treatments with thrombin dose-dependently increased the steady state levels of PAI-1 mRNA and the generation of PAI-1 antigen from BASMC. Thrombin receptor-activating peptide mimicked the effect of thrombin on the generation of PAI-1. Sodium fluoride (1 mM) stimulated PAI-1 generation from BASMC. Pertussis toxin dose-dependently suppressed thrombin-induced increase of PAI-1 generation. Treatment with 5 mM neomycin, 10 microM U73122 or 1 microM calphostin C blocked thrombin-induced PAI-1 generation. Phorbol myristate acetate at 10 nM for 3 h strongly stimulated the generation of PAI-1 from BASMC. Forskolin (100 microM) or 8-bromo-cAMP (100 microM) suppressed thrombin-induced PAI-1 generation. The responses of quiescent BASMC to thrombin or the inhibitors on PAI-1 generation were comparable to that of growing cells. The results of the present study suggest that pertussis toxin-sensitive G proteins and a phospholipase C are involved in thrombin-induced generation of PAI-1 in BASMC, which may transmit signals from occupi...Continue Reading

Citations

Jul 19, 2005·International Immunopharmacology·Kriti Rakesh, Devendra K Agrawal
Jul 6, 2000·British Journal of Pharmacology·Z Mallat, A Tedgui
Aug 23, 2002·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·H K F Lau, J Ho

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