| 研究実績の概要 |
Aim: Corticotropin-releasing hormone (CRH) and its receptors play important roles in colonic response to stress. We tested the hypothesis that peripheral CRH receptor 1 (CRH-R1) activation induces colonic visceromotor dysfunction as well as anxiety behavio. Methods: Male Wistar rats were divided into four groups. Either vehicle or CRH-R1 antagonist (CP-154,526) was injected subcutaneously 30 min before intraperitoneal injection of CRH-R1 agonist cortagine or vehicle. Colorectal distention (CRD) was performed two times over 20 minutes. The electromyogram (EMG) was recorded to measure the visceromotor responses (VMR) to CRD. Anxiety-related behavior was measured for 5 minutes during exposure to an elevated-plus maze (EPM). Results: Compared with vehicle, cortagine significantly induced increase in fecal pellets number (P < 0.05). CP-154,526 abolished the cortagine-induced fecal pellets output (P < 0.05). The amplitude of EMG has significant differences among four groups (P < 0.01). In the rats treated with cortagine, EMG amplitude was significantly higher than that control and CP group (P < 0.05). CP-154,526 has significantly decreased amplitude, compared with cortagine group (P < 0.05). The total travel distance in the EPM has significantly differences among four groups (P = 0.01). Conclusions: Our results suggest that peripheral cortagine injection can stimulate defecation and induce visceral hypersensitivity in rats, which were abolished by CRH-R1 antagonist. Peripheral cortagine may induce anxiety-related behaviour while CRH-R1 antagonist reduces the anxiety behavior.
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