Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon

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 (0.1 nM - 3 muM) and SFLLRN-NH2 (1 nM - 3 muM), and PAR-2 agonists, trypsin (0.1 nM - 10 muM) and SLIGRL-NH2 (1 nM - 10 muM), 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 muM) indicating that they mainly occur via activation of Ca2+-dependent small conductance, K+-channels. 5 The responses to PAR-1 and PAR-2 were unaffected by tetrodotoxin (1 muM) or indomethacin (1 muM) 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.