RELAXANT AND CONTRACTILE RESPONSES OF PORCINE PULMONARY-ARTERIES TO THROMBIN AND THROMBIN RECEPTOR ACTIVATING PEPTIDES

The vascular effects of thrombin and thrombin receptor activating pept ides (TRAP) were studied on isolated rings from porcine pulmonary arte ries. In prostaglandin F-2 alpha (PGF(2 alpha)) -precontracted vessels with intact endothelium, both thrombin- and TRAP-induced nitric oxide -mediated relaxation, whereas in endothelium-denuded vessels thrombin and TRAP elicited concentration-dependent contractile responses. The f irst phasic component of contraction was associated with increased gen eration of inositol 1,4,5-triphosphate and the tonic component seemed to be due to the activation of protein kinase C. Both peptides (TRAP-6 with 6 and TRAP-14 with 14 amino acid residues) did not differ in the ir intrinsic activity; like thrombin, both peptides elicited dualistic vascular effects but their potency was more than three orders of magn itude less than that of thrombin.