Substance-P-mediated intestinal inflammation: inhibitory effects of CP 96,345 and SMS 201-995.
The proinflammatory peptide substance P (SP) has been shown to be intimately involved in the local inflammatory processes of Trichinella-spiralis-induced murine intestinal inflammation. Significant increases in SP, increased myeloperoxidase levels coupled with local morphological deterioration of the jejunum and impaired lymphocyte responses to exogenous SP in vitro have been associated with the model. We have recently determined that the elimination of increased levels of SP via anti-SP antibody therapy can spare the murine gastrointestinal tract much of the pathologies associated with the parasitic infection. Here we further demonstrate that the somatostatin analogue SMS 201-995 as well as the SP receptor antagonist CP 96,345 can effectively decrease the inflammation and lost lymphocyte function seen in the jejunum of T. spiralis-infected mice. Again, both intestinal morphology and myeloperoxidase levels were shown to return to normal values upon treatment. The above results suggest that SP is an important modulator of gastrointestinal inflammation.
Kataeva
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Intestinal Diseases Research Programme, McMaster University, Hamilton, Ont., Canada.
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Stanisz
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007249:Inflammation; D007411:Intestinal Diseases, Parasitic / Q000188:drug therapy / Q000503:physiopathology*; D007583:Jejunum / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000201:enzymology; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D009195:Peroxidase / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000188:drug therapy / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D013373:Substance P; D009195:Peroxidase; D015282:Octreotide; C066892:CP 96345