title: Urocortins and CRF type 2 receptor isoforms expression in the rat stomach are regulated by endotoxin: role in the modulation of delayed gastric emptying.
abstract: Peripheral activation of corticotropin-releasing factor receptor type 2 (CRF(2)) by urocortin 1, 2, or 3 (Ucns) exerts powerful effects on gastric function; however, little is known about their expression and regulation in the stomach. We investigated the expression of Ucns and CRF(2) isoforms by RT-PCR in the gastric corpus (GC) mucosa and submucosa plus muscle (S+M) or laser captured layers in naive rats, their regulations by lipopolysaccharide (LPS, 100 μg/kg ip) over 24 h, and the effect of the CRF(2) antagonist astresssin(2)-B (100 μg/kg sc) on LPS-induced delayed gastric emptying (GE) 2-h postinjection. Transcripts of Ucns and CRF(2b,) the most common wild-type CRF(2) isoform in the periphery, were expressed in all layers, including myenteric neurons. LPS increased Ucn mRNA levels significantly in both mucosa and S+M, reaching a maximal response at 6 h postinjection and returning to basal levels at 24 h except for Ucn 1 in S+M. By contrast, CRF(2b) mRNA level was significantly decreased in the mucosa and M+S with a nadir at 6 h. In addition, CRF(2a), reportedly only found in the brain, and the novel splice variant CRF(2a-3) were also detected in the GC, antrum, and pylorus. LPS reciprocally regulated these variants with a decrease of CRF(2a) and an increase of CRF(2a-3) in the GC 6 h postinjection. Astressin(2)-B exacerbated LPS-delayed GE (42-73%, P < 0.001). These data indicate that Ucn and CRF(2) isoforms are widely distributed throughout the rat stomach and inversely regulated by immune stress. The CRF(2) signaling system may act to counteract the early gastric motor alterations to endotoxemia.
authors.affiliation: CURE: Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute/UCLA, 1301 Wilshire Blvd., Los Angeles, CA 90073, USA. pqyuan@mednet.ucla.edu
authors.forename: Pu-Qing
authors.initials: PQ
authors.lastname: Yuan
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Wu
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D005753:Gastric Mucosa / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007536:Isomerism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013270:Stomach / Q000187:drug effects; D054832:Urocortins / Q000096:biosynthesis*
chemical_list: C101531:CRF receptor type 2; D004731:Endotoxins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C104416:astressin; D012313:RNA; D003346:Corticotropin-Releasing Hormone