Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats
Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats
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DOI：
10.1152/ajpgi.90557.2008
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发表时间：
2009-02-01
影响因子：
4.5
通讯作者：
Mayer, Emeran A.
中科院分区：
文献类型：
--
作者：
Bradesi, Sylvie;Martinez, Vicente;Mayer, Emeran A.
Bradesi S, Martinez V, Lao L, Larsson H, Mayer EA. Involvement of vasopressin 3 receptors in chronic psychological stressinduced visceral hyperalgesia in rats. Am J Physiol Gastrointest Liver Physiol 296: G302-G309, 2009. First published November 25, 2008; doi:10.1152/ajpgi.90557.2008.-内脏过敏和应激与功能性胃肠道疾病的病理生理学有关。我们使用选择性加压素 3 (V-3) 受体拮抗剂 SSR149415 来研究加压素 (AVP)/V-3 信号系统在大鼠应激诱导内脏痛觉过敏发生过程中的作用。 Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10-60 mmHg) was assessed before and after stress.在第11天的CRD之前，每天用SSR149415（每次WAS或假WAS会话前30分钟腹腔注射0.3、1或3 mg/kg ip）、单剂量SSR149415（1 mg/kg ip）或选择性促肾上腺皮质激素释放因子1（CRF1）拮抗剂DMP-696（30 mg/kg po）治疗动物。 of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension.这些数据支持 V-3 受体在反复心理应激引起的内脏痛觉过敏中发挥重要作用，并表明 AVP/V-3 通路的药理学操作可能是治疗慢性应激相关胃肠道疾病的 CRF/CRF1 通路的有吸引力的替代方案。
Bradesi S, Martinez V, Lao L, Larsson H, Mayer EA. Involvement of vasopressin 3 receptors in chronic psychological stressinduced visceral hyperalgesia in rats. Am J Physiol Gastrointest Liver Physiol 296: G302-G309, 2009. First published November 25, 2008; doi:10.1152/ajpgi.90557.2008.-Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V-3) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V-3 signaling system in the development of stress-induced visceral hyperalgesia in rats. Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10-60 mmHg) was assessed before and after stress. Animals were treated daily with SSR149415 (0.3, 1, or 3 mg/kg ip 30 min before each WAS or sham WAS session), with a single dose of SSR149415 (1 mg/kg ip), or the selective corticotropin-releasing factor 1 (CRF1) antagonist DMP-696 (30 mg/kg po) before CRD at day 11. Effects of a single dose of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension. These data support a major role for V-3 receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V-3 pathway might represent an attractive alternative to the CRF/CRF1 pathway for the treatment of chronic stress-related gastrointestinal disorders.