Enhanced pelvic responses to stressors in female CRF-overexpressing mice

被引:42
作者
Million, M.
Wang, L.
Stenzel-Poore, M. P.
Coste, S. C.
Yuan, P. Q.
Lamy, C.
Rivier, J.
Buffington, T.
Tache, Y.
机构
[1] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA
[2] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA
[4] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA
[5] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA
[6] Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA
关键词
chronic stress; colon; urine; locomotor activity; astressin B; mouse urocortin 2;
D O I
10.1152/ajpregu.00626.2006
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF1/CRF2 receptor antagonist astressin B and the selective CRF2 receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF1 and CRF2 receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF1-initiated colonic response is counteracted by selective activation of CRF2 receptor.
引用
收藏
页码:R1429 / R1438
页数:10
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