Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon
Article first published online: 2 FEB 2009
2002 British Pharmacological Society
British Journal of Pharmacology
Volume 136, Issue 3, pages 367–374, June 2002
How to Cite
Mulè, F., Baffi, M. C. and Cerra, M. C. (2002), Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon. British Journal of Pharmacology, 136: 367–374. doi: 10.1038/sj.bjp.0704746
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- (Received February 25, 2002, Accepted April 4, 2002)
- Protease-activated receptor (PAR);
- intestinal motility;
- rat colon;
- potassium channel
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.
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).
Both PAR-1 agonists, thrombin (0.1 nM – 3 μM) and SFLLRN-NH2 (1 nM – 3 μM), and PAR-2 agonists, trypsin (0.1 nM – 10 μM) and SLIGRL-NH2 (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.
The inhibitory effects were greatly reduced or abolished by apamin (0.1 μM) indicating that they mainly occur via activation of Ca2+-dependent small conductance, K+-channels.
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.
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.
British Journal of Pharmacology (2002) 136, 367–374; doi:10.1038/sj.bjp.0704746