title: Chronic inflammation alters the contribution of neurokinin receptor subtypes to epithelial function in rat colon.
abstract: We have previously shown that neurokinin-1 (NK1) receptors predominantly mediate substance P-induced secretion of the non-inflamed rat colonic mucosa in vitro with a gradient in the magnitude of these responses. The aim of this study was to examine the effects of chronic inflammation on the contributions of different neurokinin receptor subtypes to colonic mucosal secretion. Colitis was induced by the intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid in rats, reactivated 6 weeks later. Segments of proximal, mid- and distal colon were stripped of muscularis propria and mounted in Ussing chambers for measurement of short-circuit current. Use of selective agonists suggests that in the chronically inflamed rat colon NK1 receptors play a greater role in neurokinin-mediated mucosal secretion than do either NK2 or NK3. Selective antagonism implies that this is region-specific, with the inflammatory process altering the relative contribution of the neurokinin receptor subtypes within each region of the rat colon.
authors.affiliation: Department of Physiology & Pharmacology, Ponce School of Medicine, Ponce, PR 00732-7004, USA. cappleyard@psm.edu
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Appleyard
authors.forename: Marangelie
authors.initials: M
authors.lastname: Morales
authors.forename: Cariluz
authors.initials: C
authors.lastname: Santiago
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013373:Substance P / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014150:Antipsychotic Agents; D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C085215:SR 140333; D013373:Substance P; D013779:Tetrodotoxin; C073839:SR 48968; D015288:Neurokinin A; D014302:Trinitrobenzenesulfonic Acid; C091554:SR 142801; D007213:Indomethacin