Involvement of pertussis toxin-sensitive and -insensitive G proteins in alpha-thrombin signalling on cultured human vascular smooth muscle cells.
Alpha-thrombin, a key enzyme of the coagulation cascade, is also a potent mitogen for human vascular smooth muscle cells (HVSMC). Here it is demonstrated that the alpha-thrombin-mediated reduction of intracellular cAMP levels is sensitive to pertussis toxin (PTX). cAMP-elevating agents inhibited alpha-thrombin- and serum-induced mitogenesis, thus cAMP confers an anti-mitogenic signal on HVSMC. The PTX-dependent ADP-ribosylation of a 41 kDa Gi alpha protein(s) was significantly inhibited (up to 55%) by thrombin. HVSMC membranes had an intrinsic GTP'ase activity which was significantly increased (up to 36%) by thrombin. PTX treatment did not alter thrombin-induced elevation of GTP'ase activity. Thrombin stimulated phosphatidyl inositol (PI) turnover in a PTX-insensitive manner. This suggested that PTX insensitive G proteins such as Gq are also activated by thrombin. This study on HVSMC provides additional evidence for the involvement of different families of G proteins in thrombin signalling.
Kanthou
C
C
Thrombosis Research Institute, Chelsea, London, UK.
Kanse
S M
SM
Kakkar
V V
VV
Benzakour
O
O
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010716:Phosphatidylinositols; D012503:Saponins; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin; D013917:Thrombin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000527:Alprostadil; D015056:1-Methyl-3-isobutylxanthine