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Thrombin-stimulated events in cultured vascular smooth-muscle cells.
- Source :
-
The Biochemical journal [Biochem J] 1991 Mar 15; Vol. 274 ( Pt 3), pp. 799-805. - Publication Year :
- 1991
-
Abstract
- Thrombin is present in high concentrations at sites of clots and may have important post-clotting effects on adjacent vascular tissue. This may be particularly important for vascular smooth-muscle cells (VSMC), whose growth and contractility are altered following atherosclerotic-associated thromboses. To study the cellular signal events by which thrombin exerts its actions, the effects of purified human alpha-thrombin were examined in cultured rat aortic VSMC. alpha-Thrombin stimulated a biphasic change in intracellular pH (pHi), causing an early rapid acidification, followed by a sustained alkalinization. The increase in pHi was dependent on extracellular Na+ and inhibited by 5'-(NN-dimethyl)amiloride, consistent with mediation by Na+/H+ exchange. alpha-Thrombin rapidly increased free intracellular [Ca2+] ([Ca2+]i). The increase in [Ca2+]i was secondary to activation of phospholipase C, as demonstrated by increases in InsP3 (226%) and InsP2 (387%) and decreases in polyphosphoinositides at 15 s. Expression of the mRNA for the proto-oncogene c-fos was induced by alpha-thrombin. Stimulation of c-fos mRNA was not dependent on alterations in pHi, but required a rise in [Ca2+]i. Despite many growth-related signals shared by alpha-thrombin with platelet-derived growth factor, alpha-thrombin failed to stimulate [3H]thymidine incorporation or cell division, although there was a maximal increase of 52% in protein synthesis. The data suggest that there are cellular signal events not activated by alpha-thrombin which are required for proliferation of these aortic VSMC.
- Subjects :
- Animals
Blotting, Northern
Calcium metabolism
Cells, Cultured
Hydrogen metabolism
Hydrogen-Ion Concentration
Hydrolysis
Inositol Phosphates metabolism
Male
Muscle Contraction
Muscle Development
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular growth & development
Nucleic Acid Hybridization
Phospholipids metabolism
Proto-Oncogene Mas
RNA, Messenger analysis
RNA, Messenger genetics
Rats
Rats, Inbred Strains
Sodium metabolism
Thrombosis metabolism
Thrombosis physiopathology
Type C Phospholipases metabolism
Muscle, Smooth, Vascular physiopathology
Thrombin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 274 ( Pt 3)
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 2012607
- Full Text :
- https://doi.org/10.1042/bj2740799