Treatment with neurokinin-1 receptor antagonist reduces severity of inflammatory bowel disease induced by Cryptosporidium parvum.
Inflammatory bowel disease (IBD) is a chronic, debilitating disorder of uncertain and perhaps multiple etiologies. It is believed to be due in part to disregulation of the immune system. Neuroimmune interactions may be involved in induction or maintenance of IBD. In the present study, we examined the potential role of a neurotransmitter, substance P, in a mouse model of IBD. We found that binding sites for substance P, and more specifically, neurokinin-1 receptors, were upregulated in intestinal tissue of mice with IBD-like syndrome. Dosing of mice with LY303870, a neurokinin-1 receptor antagonist, reduced the severity of IBD, and treatment of mice with preexisting IBD allowed partial healing of lesions. We hypothesize that blocking the binding of substance P to the neurokinin-1 receptor interrupts the inflammatory cascade that triggers and maintains intestinal lesions of IBD.
Sonea
Ioana M
IM
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011, USA. ioana@iastate.edu
Palmer
Mitchell V
MV
Akili
Dhuha
D
Harp
James A
JA
D000818:Animals; D001345:Autoradiography; D002417:Cattle; D003457:Cryptosporidiosis / Q000150:complications* / Q000473:pathology; D016785:Cryptosporidium parvum; D004195:Disease Models, Animal; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000235:genetics
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018040:Receptors, Neurokinin-1