Abstract
We studied the actions of the human and murine proteinase-activated receptor 4 (PAR
4
) derived receptor-activating peptides (APs), GYPGQV-NH
2
(GQV-NH
2
) and GYPGKF-NH
2
(GKF-NH
2
), (i) to activate-desensitize either PAR
1
or PAR
2
in cultured cell systems (calcium signalling in PAR
1
/PAR
2
-bearing human HEK cells and in rat KNRK cells expressing either rat or human PAR
2
) and (ii) to affect contractility in rat aorta (RA) and rat gastric longitudinal muscle (LM) preparations in vitro. We found that neither PAR
1
nor PAR
2
was affected by concentrations of the PAR
4
-APs (800 µM) that caused both an endothelium-dependent nitric oxide mediated relaxation of preconstricted RA tissue and a contractile response in the LM preparation. The potencies (EC
50
values 300 to 400 µM) of GQV-NH
2
and GKF-NH
2
for causing a relaxant effect were identical and comparable with the potency of GQV-NH
2
for causing a contractile effect in the LM. However, the potencies of the PAR
4
-APs in the RA and LM preparations were 20- to 150-fold lower than the potency of the receptor-selective PAR
1
-AP, TFLLR-NH
2
. We conclude that the PAR
4
-APs do not activate either PAR
1
or PAR
2,
and we suggest that along with PAR
1
and PAR
2
, PAR
4
may also be present in rat vascular and gastric smooth muscle.Key words: proteinase-activated receptors, PAR
4
, calcium, vascular smooth muscle, gastric smooth muscle, thrombin.