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Enhanced mucosal permeability and nitric oxide synthase activityin jejunum of mast cell deficient mice |
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| Authors: | S Komatsu M Grisham J Russell D Granger |
| Affiliation: | Department of Physiology, LSU Medical Center, Shreveport 71130-3932, USA. |
| Abstract: | Background—Recent reports have described amodulating influence of nitric oxide (NO) on intestinal mucosalpermeability and have implicated a role for mast cells in this NOmediated process. Aims—To assess further the contribution of mastcells to the mucosal permeability changes elicited by the NO synthase(NOS) inhibitor NG-nitro-L-arginine methylester(L-NAME), using mast cell deficient (W/WV) andmast cell replete mice (+/+). Methods—Chromium-51 EDTA clearance (from blood tojejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, andplasma nitrate/nitrite levels were monitored. Results—The increased EDTA clearance elicited byintraluminal L-NAME in W/WV mice (4.4-fold) wassignificantly greater than the response observed in control (+/+) mice(1.8-fold). The exacerbated response in W/Wv mice wasgreatly attenuated by pretreatment with either dexamethasone (1.3-fold)or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold),and partially attenuated by the mast cell stabiliser, lodoxamide(2.9-fold). Jejunal inducible NOS activity was significantly higher inW/WV than in +/+ mice, while jejunal MPO was lower inW/WV mice than in +/+ mice, suggesting that the higherinducible NOS in W/WV does not result from the recruitmentof inflammatory cells into the gut. The higher inducible NOS activityin the jejunum of W/WV was significantly reduced bydexamethasone treatment. Conclusions—Our results suggest that mast cellsnormally serve to inhibit inducible NOS activity tonically in the gutand that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion. Keywords:aminoguanidine; c-kit; dexamethasone; epithelium; neutrophils |
| Keywords: | aminoguanidine c-kit dexamethasone epithelium neutrophils |