title: Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis.
abstract: It is becoming increasingly evident that the urocortins (Ucns) and their receptors are involved in the initiation and development of inflammation in the gastrointestinal (GI) tract. There has not been a systematic study of the basal expression of Ucns or their receptors in the GI tract. Here, we examined basal expression of Ucn 2 and its high-affinity receptor, CRF-R2 in the rat GI tract. Ucn 2 mRNA was expressed throughout the small and large intestine. Surprisingly, CRF-R2 mRNA expression was detected in only a subset of GI regions that expressed Ucn 2. Immunohistochemical study showed that both Ucn 2 immuno-reactivity (Ucn 2-IR) and CRF-R2-IR were consistently seen in the neurons of the myenteric plexus and the nerve fibers innervating the circular muscle. By and large, Ucn 2-IR was detected in all layers, including the mucosal and the submucosal layers throughout the GI regions. In contrast, CRF-R2-IR was very low or undetectable in the mucosal layers of all regions examined. The role of Ucn 2 and CRF-R2 was then examined in a rat model of chemically-induced colitis. In the early phase of colitis, Ucn 2 mRNA levels peaked, whereas, in striking contrast, CRF-R2 mRNA expression decreased approximately 2.5-fold below control levels. At the peptide level, Ucn 2-IR was specifically induced in a large population of immune cells that infiltrated the lamina propria and submucosa of the distal colon, whereas CRFR2-IR was detected in only a small fraction of infiltrated immune cells. CRF-R2-IR was dramatically reduced in the neurons of the myenteric plexus. Thus, we show, for the first time, that in the acute phase of inflammation, Ucn 2 levels are increased whereas expression levels of its only identified receptor, CRF-R2, are decreased. This suggests that Ucn 2 exerts its effects only in part via CRF-R2.
authors.affiliation: Department of Surgery, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Jen
authors.initials: J
authors.lastname: Chang
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Hoy
authors.forename: Prema S
authors.initials: PS
authors.lastname: Idumalla
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Clifton
authors.forename: Norman C
authors.initials: NC
authors.lastname: Pecoraro
authors.forename: Aditi
authors.initials: A
authors.lastname: Bhargava
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C514216:urocortin 3, rat; D014302:Trinitrobenzenesulfonic Acid; D003346:Corticotropin-Releasing Hormone