EFFECTS OF THROMBIN RECEPTOR ACTIVATING PEPTIDE ON PHOSPHOINOSITIDE HYDROLYSIS AND PROTEIN-KINASE-C ACTIVATION IN CULTURED RAT AORTIC SMOOTH-MUSCLE CELLS - EVIDENCE FOR TETHERED-LIGAND ACTIVATION OF SMOOTH-MUSCLE CELL THROMBIN RECEPTORS

Phosphoinositide hydrolysis and protein kinase C (PKC) activation were examined in response to treatment of rat aortic smooth muscle cells w ith alpha-thrombin and a seven amino acid thrombin receptor activating peptide (TRAP-7; SFLLRNP). Alpha-thrombin and TRAP-7 stimulated total inositol phosphate (IP) accumulation and phosphorylation of a specifi c endogenous substrate for activated PKC. Acetylated TRAP-7 and ''reve rse'' TRAP (FSLLRNPNDKYEPF) were ineffective in stimulating signal tra nsduction. The active site inhibitor, MD805 (argatroban), and the anio n-binding exosite inhibitor, BMS 180,742, reduced the IP response to a lpha-thrombin in a concentration-dependent manner. In contrast, the TR AP-7-induced IP response was not affected by either inhibitor. These d ata are consistent with the tethered-ligand hypothesis for thrombin re ceptor activation in rat aortic smooth muscle cells.