Up-regulation of PAR-1 and PAR-2 expression contributes to nematode-induced hypercontractility of murine intestinal smooth muscle

Abstract

Musculans whole mounts of the intestine were stained for myelopemxidase (MPO)-positive leukocytes. Sterile intestinal muscle preparations were incubated for 24h and tissue culture supematants assayed for NO By the Griess reaction (~M/100mg'tissue) Data are mean -+ SEM, N =4-5. Results: Yoh significantly decreased the IM-induced delay in gastrointestinal transit without affecting transit in controls (GC: control-veh 8.9 + 0.3, control-Yoh 9 7 -+ 0.2, IM-veh 6 7 + 0.8, IM-Yoh 8.6 + 0.3). Yoh significantly improved the IM-induced suppression of in vgro contractility, which was not attenuated by vehicle (contractility at 100p.M Bethanechol g/s/ram2: control-veh 4 12 _+ 0 99, control-Yoh 4.15 -+ 0 79, iM/veh 2.16 _+ 0 68, IMYoh 2.84 -+ 0.93). The muscularis leukocyte infiltrate that increased after IM was not affected by Yoh (MPO-posinve cells/ field: control-veh 1.2-+0.2, control-Yoh 1.1 +-0.2, IM-veh 617 -+ 148,1M-Yoh 69.0--+ 10 1). NO production increased 5.6 fold after IM in tissue culture supematants. This increase was completely inhibited by the selective iNOS inhibitor L-NiL Yohimbine attenuated the increase after IM by 35% (NO control-veh = 5.46 _+ 0.59, controlY o h = 6 . 1 2 + 1.00, l M v e h = 3 f l . 3 7 _ + 1.36, IM-veh with L N I L = 8 9 4 0 + . 1 7 , IMYoh = 19.83 -+ 5.8). Conclusion: This study suggests that the effect of alpha-2 adrenoreceptor stimulation on the development of postoperative ileus is in part mediated through alpha-2 adrenergic regulation of post-surgical NO production within the intestinal muscularis.