Rotavirus Infection of Murine Small Intestine Causes Colonic Secretion via Age Restricted Galanin-1 Receptor Expression

Background & Aims: Mechanisms for age restriction of rotavirus diarrhea are unclear. Because rotavirus primarily infects small intestine, colonic contribution has not been widely studied. Recent data suggest that colonic secretion postbacterial infection is mediated by galanin-1 receptors (Gal1-R). We evaluated age-dependent expression of Gal1-R in Rhesus rotavirus (RRV)-infected mice and its contribution to fluid secretion. Methods: Twenty-four hours after infection of C57BL/6J mice (wild type or Gal1-R knockout) with RRV or vehicle, closed small intestinal and colon loops were constructed. Net fluid content of the loops was calculated (milligrams/centimeters) at 2 hours post-treatment with galanin, galanin antibody, or lidocaine. Gal1-R expression was quantified by automated chromogen analysis. Results: Viral antigen was detected in small intestinal epithelial cells but not in colon. Developmental Gal1-R was widely expressed in the small intestine but minimally in the colon. Postinfection, markedly increased Gal1-R was seen in the colon but not after day 25. Galanin caused a significantly higher increase in the net fluid content of infected colon than small intestine. Treatment with lidocaine reduced net fluid secretion in the small intestine and the colon. Mean diarrheal scores were significantly reduced in Gal1-R knockout mice compared with wild type (1.19 ± 0.31, n = 22 vs 3.36 ± 0.50, n = 35, P = .0001). Conclusions: These data show that RRV infection of the small intestine increases colonic secretion through Gal1-R and provide a promising start toward understanding the age restriction of rotavirus diarrhea.