Urocortins and CRF type 2 receptor isoforms expression in the rat stomach are regulated by endotoxin: role in the modulation of delayed gastric emptying

Yuan PQ, Wu SV, Tache Y. Urocortins and CRF type 2 receptor isoforms expression in the rat stomach are regulated by endotoxin: role in the modulation of delayed gastric emptying. Am J Physiol Gastrointest Liver Physiol 303: G20-G31, 2012. First published April 19, 2012; doi:10.1152/ajpgi.00547.2011.-Peripheral activation of corticotropin-releasing factor receptor type 2 (CRF2) 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 CRF2 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 mu g/kg ip) over 24 h, and the effect of the CRF2 antagonist astresssin(2)-B (100 mu g/kg sc) on LPS-induced delayed gastric emptying (GE) 2-h postinjection. Transcripts of Ucns and CRF2b, the most common wild-type CRF2 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, CRF2b mRNA level was significantly decreased in the mucosa and M + S with a nadir at 6 h. In addition, CRF2a, reportedly only found in the brain, and the novel splice variant CRF2a-3 were also detected in the GC, antrum, and pylorus. LPS reciprocally regulated these variants with a decrease of CRF2a and an increase of CRF2a-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 CRF2 isoforms are widely distributed throughout the rat stomach and inversely regulated by immune stress. The CRF2 signaling system may act to counteract the early gastric motor alterations to endotoxemia.