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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.
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
February 2000,
Thrombosis research,
B C Berk, and
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E J Cragoe, and
J W Fenton, and
T A Brock
March 1992,
Rinsho byori. The Japanese journal of clinical pathology,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
November 1991,
Thrombosis research,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
April 1989,
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B C Berk, and
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K K Griendling, and
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T A Brock
September 1995,
Biological & pharmaceutical bulletin,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
September 2000,
American journal of physiology. Heart and circulatory physiology,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
May 1988,
Biochemical and biophysical research communications,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
October 1995,
Circulation research,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
June 1997,
Blood,
B C Berk, and
M B Taubman, and
K K Griendling, and
E J Cragoe, and
J W Fenton, and
T A Brock
March 1997,
Arteriosclerosis, thrombosis, and vascular biology,
