1 Protease-activated receptors (PARs) 1 and 2 modulate the gastric and inte
stinal smooth muscle motility in vitro. In the present study, we examined i
f activation of PAR-2 and PAR-1 could alter gastrointestinal transit in mic
2 Intraperitoneal administration of the PAR-2-activating peptide SLIGRL-NH2
, but not the inactive control LSIGRL-NH2, at 1-5 mu mol kg(-1), in combina
tion with the aminopeptidase inhibitor amastatin at 2.5 mu mol kg(-1), faci
litated gastrointestinal transit in a dose-dependent manner. The human PAR-
1-derived peptide SFLLR-NH2 and the specific PAR-1 agonist TFLLR-NH2, but n
ot the inactive control FSLLR-NH2, at 2.5 - 10 pmol kg(-1), in combination
with amastatin, also promoted gastrointestinal transit.
3 The Ca2+-activated, small conductance K+ channel inhibitor apamin at 0.01
mu mol kg(-1) significantly potentiated the actions of SLIGRL-NH2 and TFLL
R-NH2 at subeffective doses.
4 The increased gastrointestinal transit exerted by either SLIGRL-NH2 at 5
mu mol kg(-1) or TFLLR-NH2 at 10 mu mol kg(-1) was completely abolished by
the L-type Ca2+ channel inhibitor verapamil at 61.6 mu mol kg(-1). In contr
ast. the tyrosine kinase inhibitor genistein at 18.5 mu mol kg(-1) failed t
o modify the effects of the agonists for PAR-2 or PAR-1.
5 These findings demonstrate that PAR-I and PAR-2 modulate gastrointestinal
transit in mice in vivo. Our data also suggest that the PAR-1-and PAR-2-me
diated effects are modulated by apamin-sensitive K+ channels and are depend
ent on activation of L-type Ca2+ channels, but independent of tyrosine kina
se. Our study thus provides novel evidence for the physiological and/or pat
hophysiological roles of PARs 1 and 2 in the digestive systems, most probab
ly during inflammation.