INVOLVEMENT OF PERTUSSIS-TOXIN-SENSITIVE AND PERTUSSIS-TOXIN-INSENSITIVE G-PROTEINS IN ALPHA-THROMBIN SIGNALING ON CULTURED HUMAN VASCULAR SMOOTH-MUSCLE CELLS

alpha-thrombin, a key enzyme of the coagulation cascade, is also a pot ent mitogen for human vascular smooth muscle cells (HVSMC). Here it is demonstrated that the alpha-thrombin-mediated reduction of intracellu lar cAMP levels is sensitive to pertussis toxin (PTX). cAMP-elevating agents inhibited alpha-thrombin-and serum-induced mitogenesis, thus cA MP confers an anti-mitogenic signal on HVSMC. The PTX-dependent ADP-ri bosylation of a 41 kDa G(i alpha) protein(s) was significantly inhibit ed (up to 55%) by thrombin. HVSMC membranes had an intrinsic GTP'ase a ctivity which was significantly increased (up to 36%) by thrombin. PTX treatment did not alter thrombin-induced elevation of GTP'ase activit y. Thrombin stimulated phosphatidyl inositol (PI) turnover in a PTX-in sensitive manner. This suggested that PTX insensitive G proteins such as Gq are also activated by thrombin. This study on HVSMC provides add itional evidence for the involvement of different families of G protei ns in thrombin signalling.