cp-154526 has been researched along with Dilatation--Pathologic* in 2 studies
2 other study(ies) available for cp-154526 and Dilatation--Pathologic
Article | Year |
---|---|
Injection of corticotropin-releasing hormone into the amygdala aggravates visceral nociception and induces noradrenaline release in rats.
Corticotropin-releasing hormone (CRH) and its receptor 1 (CRH-R1) play an important role in the colonic response to stress. The central nucleus of the amygdala (CeA) is a major extrahypothalamic site that contains a large number of neurons expressing both CRH and CRH-R1. Here, we verified the hypothesis that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline, dopamine, and serotonin (5-HT) in the CeA.. In male Wistar rats, visceral sensitivity was quantified by recording the visceromotor response to colorectal distension (CRD) with administration of vehicle, CRH, or the CRH-R1 antagonist CP-154526+ CRH or CRH-R1 antagonist CP-154526 alone into the CeA. Simultaneously, extracellular levels of noradrenaline, dopamine, and 5-HT were measured in the CeA using microdialysis. All data were obtained under restraint conditions.. Administration of CRH into the CeA significantly increased the number of abdominal muscle contractions in response to CRD. CP-154526 significantly blocked the number of abdominal muscle contractions in response to CRD with the administration of CRH into the CeA. Noradrenaline in the CeA was increased by CRD, further increased by CRH, and inhibited by CRH-R1 antagonist. Dopamine in the CeA was also exaggerated by CRH but was not inhibited by CRH-R1 antagonist. 5-HT in the CeA was unchanged.. These results suggest that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline. Topics: Amygdala; Animals; Colon; Corticotropin-Releasing Hormone; Dilatation, Pathologic; Dopamine; Male; Nociception; Norepinephrine; Pyrimidines; Pyrroles; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Rectum; Serotonin | 2015 |
Corticotropin-releasing hormone receptor 1 antagonist blocks colonic hypersensitivity induced by a combination of inflammation and repetitive colorectal distension.
Gastroenteritis is one of the risk factors for developing irritable bowel syndrome (IBS). However, the precise mechanism of postinfectious IBS is still unknown. We tested the hypothesis that a combination of previous inflammation and repetitive colorectal distention (CRD) makes the colon hypersensitive and that treatment with a corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist blocks this colonic hypersensitivity. Rats were pretreated with vehicle or 2,4,6-trinitrobenzene sulphonic acid (TNBS) 6 weeks before CRD. For the CRD experiment, the colorectum was distended once a day for six consecutive days. The CRH-R1 antagonist (CP-154,526, 20 mg kg(-1)) or vehicle was injected subcutaneously 30 min before CRD. Visceral perception was quantified as visceromotor response (VMR) using an electromyograph. For histological examination, the rats were killed on the last day of CRD experiment, and haematoxylin and eosin-staining of colon segments was performed. Although from the first to the third day of CRD, VMRs increased in both the vehicle-treated rats and TNBS-treated rats, they were significantly higher in TNBS-treated rats than those in vehicle-treated controls. On the fifth day of CRD, however, VMRs in the vehicle-treated rats were significantly greater than those in TNBS-treated rats. Pretreatment of rats with CP-154,526 significantly attenuated the increase in VMR induced by repetitive CRD with previous inflammation. Finally, we found that repetitive CRD and repetitive CRD after colitis induced visceral inflammation. These results indicate that a combination of previous inflammation and repetitive CRD induces visceral hypersensitivity and that a CRH-R1 antagonist attenuates this response in rats. Topics: Animals; Colitis; Colon; Dilatation, Pathologic; Electromyography; Humans; Inflammation; Irritable Bowel Syndrome; Male; Pyrimidines; Pyrroles; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Trinitrobenzenesulfonic Acid | 2008 |