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1 The present study examined the mechanical effects of agonist enzymes and receptor-activating peptides for protease-activated receptor (PAR)-1 and PAR-2 on longitudinal and circular muscle of rat isolated colonic segments in the attempt to clarify the PAR functional role in intestinal motility. 2 The responses to PAR-1 and PAR-2 activation were examined in vitro by recording simultaneously the changes of endoluminal pressure (index of circular muscle activity) and of isometric tension (index of longitudinal muscle activity). 3 Both PAR-1 agonists, thrombin (O.1 nM - 3μM) and SFLLRN-NH[sub2]; (1 nM-3 μM), and PAR-2 agonists, trypsin (0.1 nM-10 μM) and SLIGRL-NH[sub2]; (1 nM-10 μM), induced different effects in the two muscular layers: a reduction of the spontaneous contractions in the circular muscle and a contractile effect or biphasic, relaxation followed by contraction, depending on the concentration, in the longitudinal muscle. 4 The inhibitory effects were greatly reduced or abolished by apamin (0.1 μM) indicating that they mainly occur via activation of Ca[sup2-]-dependent small conductance, K-channels. 5 The responses to PAR-1 and PAR-2 were unaffected by tetrodotoxin (1 μM) or indomethacin (1 μM) suggesting that are independent by products of cyclooxygenase or by neural action potentials. 6 These findings indicate that both PAR-1 and PAR-2 are functionally expressed in rat colon. PARs mediate changes of the mechanical activity of longitudinal and circular muscle which might explain the alterations of colonic motility observed during inflammatory conditions. [ABSTRACT FROM AUTHOR]